Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Behaviors and Mental Disorders

Substance Related Disorders

Breast Neoplasms

Cognitive Dysfunction

Chemotherapy-Related Cognitive Impairment

Breast Diseases

Skin Diseases

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Quality of Life

ICOnnecta't is a stepped-care digital intervention tailored to breast cancer patients' psychosocial needs. It consists of four levels:

1. rst level. Psychosocial Screening and Monitoring: Patients assess their emotional distress and symptoms; consultations with a health psychologist are scheduled if distress is high.
2. nd level. Campus (Psychoeducation and Health Education): Patients access educational resources covering medical information, emotional well-being, relationships, and healthy habits.
3. r level. Community Psychosocial Support: Patients engage in an online community to share experiences and concerns under supervision.
4. th level. Online Group Psychotherapy: Patients participate in online group psychotherapy sessions led by a psycho-oncology specialist.

ICOgnition enhances ICOnnecta't with a Cognitive Module, following the same stepped-structure and specifically addressing cognitive deficits in breast cancer patients. It includes:

1. rst level. Cognitive Screening and Monitoring: Patients complete monthly cognitive assessments and online objective cognitive tests. If scores indicate impairment, they advance to the next level.
2. nd level. Cognitive Psychoeducational Campus: Patients undergo psychoeducation focusing on cognitive impairment understanding, behavioural strategies to enhance cognitive functioning, and acceptance strategies through mindfulness and metaphors.
3. rd level. Online Cognitive Training: Individual 30-minute online cognitive training sessions are conducted twice a week for 12 weeks, targeting specific cognitive skills. Sessions are facilitated through the CogniFit program, integrated with the ICOnnecta't App.

The ICOgnition intervention for breast cancer patients consists of three levels:

Level 1: Monthly assessments using FACT-Cog PCI and Cognifit. Scores \<54 (PCI) or ≤250 (Cognifit) escalate to Level 2.

Level 2: Specialized content includes Cognitive Psychoeducation, validating experiences and improving health literacy; Behavioral Guidance, offering practical strategies for daily tasks; and Embracing Cognitive Deficits, promoting self-compassion and acceptance through mindfulness and metaphors.

Level 3: Online cognitive training focuses on enhancing cognitive skills through gaming exercises, completing the comprehensive intervention approach.

ICOgnition

Maria Serra Blasco, PhD

Arnau Souto Sampera, MSc

Cristian Ochoa Arnedo, PhD

This study investigates the effectiveness of integrating a cognitive rehabilitation module into a digital psychosocial intervention for recently diagnosed breast cancer patients. The trial involves 176 participants, with one group receiving the ICOnnecta't program (stepped psychosocial intervention) and the other receiving ICOnnecta't with an additional cognitive stepped intervention called ICOgnition. ICOgnition has three levels of intervention including cognitive screening and monitoring, psychoeducation, and online cognitive training. Assessments of the study outcomes will be conducted at baseline, 3 months, 6 months, and 1 year, measuring cognitive functioning, emotional well-being, medication adherence, work functioning, and overall quality of life. The study aims to improve understanding of efficient ways to detect cognitive dysfunction in cancer patients and assess the benefits and feasibility of this early intervention for managing cognitive impairment in breast cancer patients.

BACKGROUND

Breast cancer (BC) diagnoses have increased, and while survival rates have improved, the focus on the quality of life (QoL) for survivors, including cognitive function, has intensified. Cancer-related cognitive impairment (CRCI) is recognized, encompassing objective deficits and subjective experiences. Various factors, such as chemotherapy agents, stress, and psychological factors, influence CRCI. Non-pharmacological treatments, including psychoeducational interventions and cognitive training, have shown promise. However, there are barriers in oncological settings, including a lack of awareness and standardized protocols. Current developed technologies like eHealth offer solutions, yet studies addressing cognitive care in eHealth psychosocial interventions are limited. This study aims to assess the ICOgnition digital intervention's effectiveness in improving BC patients' subjective and objective cognitive symptoms. It also explores factors influencing cognitive function, the effectiveness of online cognitive testing, and the gap between objective and subjective deficits. The study will also evaluate the feasibility and cost-effectiveness of ICOnnecta't + ICOgnition interventions to provide insights into their scalability and sustainability. The hypothesis suggests that the ICOnnecta't-enhanced intervention (ICOgnition) will outperform ICOnnecta't alone in improving both subjective and objective cognitive functioning in BC patients.

METHODS/DESIGN

The trial is conducted at the Catalan Institute of Oncology (ICO) in Hospitalet de Llobregat. Patients meeting inclusion criteria are referred by the Breast Functional Unit to the ICOnnecta't Program team. Eligible candidates receive detailed study information via a call and, if willing to participate, schedule an in-person appointment at the ICOnnecta't Space. Researchers explain the study, obtain informed consent, and utilize the secure web platform REDCap for questionnaires. Assessments occur at baseline (T1), 3 months (T2), 6 months (T3), and 12 months (T4). Recruitment starts in December 2023 and spans a year.

Breast cancer patients will be randomly assigned to one of the two treatment groups using REDCap, employing a simple randomization method (1:1).

o Study Sample

The study will include 176 female breast cancer patients in the acute survival phase from ICO Hospitalet.

o Statistical Analysis:

Primary Outcome Analysis

The study will employ independent Linear Mixed Models with patients clustered to analyze cognitive outcomes between the two intervention groups: digital stepped psychosocial care vs. digital stepped psychosocial care + cognitive module. Subjective Cognition (FACT-Cog) and Objective Cognition (Neurocognitive Index) will be separately assessed, adjusting for age and education. Descriptive statistics, effect sizes, and 95% confidence intervals will be reported.

Secondary Outcome Analysis

Linear Mixed Models will be used to analyze secondary outcomes (e.g., depression, anxiety, distress, quality of life) following the same procedure. Mediation analysis will explore emotional distress and posttraumatic stress as mediators between interventions and cognitive responses.

Other Pre-Specified Outcome Analyses

* Discrepancy between Objective and Subjective Measures: Standardized values will be compared using ICC, Bland-Altman Plot, and linear regression to identify variables explaining discrepancies.
* Clusters of Cognitive Impairment: Cluster analysis will identify participant groups with similar cognitive profiles and explore differences in demographics, clinical variables, and treatment response.
* Cognitive Assessment Optimization: The equivalence of online vs. paper and pencil tests in detecting cognitive impairment will be tested, and the most sensitive test for CRCI detection will be explored.
* Cost-Utility Analysis: This analysis expresses the cost-effectiveness of interventions in terms of cost per Quality-Adjusted Life Year (QALY) gained, a common measure used in healthcare decision-making.

  * Statistical Power:

Utilizing GLIPMPSE, the study has a power of 0.802 with a significance level of 0.05. With 176 subjects (88 in each group), the study can detect a significant difference of 5.9 units, assuming a common standard deviation of 15, based on previous research findings (Bell et al., 2018).

o Discussion

The ICOgnition intervention offers a promising and comprehensive approach to address cognitive difficulties in newly diagnosed breast cancer patients. By integrating digital psychosocial support, personalized cognitive training, and psychoeducational resources, this intervention aims to enhance cognitive function and improve the overall quality of life for patients. Notably, its potential impact could extend to individuals facing cognitive challenges in various medical conditions beyond breast cancer. However, challenges related to implementation, resource allocation, patient adherence, and economic evaluation need careful consideration to ensure the intervention's effectiveness in real-world settings. If successfully implemented, ICOgnition could serve as a valuable model for addressing cognitive impairments, fostering a better understanding of cognitive challenges in medical settings, and enhancing patients' overall well-being.

The study proposes a superiority RCT with two parallel groups (online psychosocial care vs. online integrated and stepped cognitive intervention) with 1:1 allocation. The study design will contain 2 (treatment conditions) × 3 (follow-up assessments) factors.

To implement masking in the outcome assessor, the study will use an external service, the Biostatistical Services of The Bellvitge Biomedical Research Institute (IDIBELL). This external service will collect information through online questionnaires using REDCap, a secure web platform. Using an external service will help maintain the integrity of the study and prevents potential biases. Blinding in this context ensures that the assessment of outcomes is conducted impartially and without any influence from knowledge about the treatment assignments.

eHealth Interventions for Breast Cancer Cognitive Impairment

Cognitive Rehabilitation and Psychosocial Intervention Through a Stepped Digital Ecosystem in Breast Cancer: A Randomized Clinical Trial.

Number of days of patients' sick leaves (Electronic Health Record).

Number of professionals involved in the ICOnnecta't treatment or ICOnnecta't + ICOgnition platform as well as the number of professionals' working hours per week and costs (Electronic Health Record).

Costs per user and per month for the development and maintenance of the ICOnnecta't + ICOgnition platform (experimental group) and costs of ICOnnecta't platform alone per user and month.

First, the Electronic Health Record will be checked to collect psychotropic medication data for each group during the study. Second, the pharmacy service of ICO will calculate the medication costs.

The Functional Assessment of Cancer Therapy-Cognitive Function, FACT-Cog, Perceived Cognitive Impairment sub-scale (PCI), developed specifically to assess cognitive difficulties in cancer patients (https://www.facit.org/measures/FACT-Cog) is used. Lower scores (0-72) indicate a poor perceived performance.

The objective cognitive assessment will be provided by the licensed computer program CogniFit Inc © 2023. CogniFit offers a specific cognitive assessment called "Chemfog," which measures 6 cognitive domains: planning, processing speed, short-term memory, focus attention, coordination and spatial perception. Lower scores (0-800) indicate poor objective performance in those domains.

Verbal Learning, Immediate Verbal Memory and Delayed Verbal Memory will be measured through RAVLT - Rey Auditory Verbal Learning Test. The executive functions domains that will be measured are cognitive flexibility through Trail Making Test B (TMT-B) \[50\], verbal fluency through its Spanish version and working memory through Digit Span backward of the Wechsler Adult Intelligence Scale IV (WAIS-IV). Attention will be measured via TMT-A and Digit Span forward (WAIS-IV). Finally, Digit Symbol Substitution Test (DSST; WAIS-IV) will be used to measure processing speed.

Hospital Anxiety and Depression Scale (HADS) will be used to assess emotional distress through 7 anxiety items (HADS-Anxiety) and 7 depression items (HADS-Depression). The range of scores is 0-21 for each subscale, and 0-42 for the overall questionnaire, where higher scores indicate worse clinical symptoms

Medication adherence will be assessed through the Spanish version of Adherence to Refill and Medication Scale (ARMS-e), which is a valid and reliable scale for patients with chronic disease. This instrument consists of 12 questions: 8 are focused on the patient's consistency in taking medication appropriately and 4 on their proper collection. Lower overall scores correspond to better adherence.

The European Quality of Life Scale (EQ-5D- 3L) provides a measure of Health-Related QoL (HRQoL) and is helpful for the evaluation of the cost-utility of health interventions. Lower scores represent worst health status.

The Post-traumatic Stress Disorder Checklist (PCL-5) is widely used in clinical and research settings to screen for post-traumatic symptoms. Higher scores indicate a higher severity of post-traumatic symptoms

Work Role Functioning Questionnaire (WRFQ): a self-report assessment tool, validated in cancer patients and in Spanish population, that is used to evaluate an individual's work-related functioning and productivity. It is specifically designed to measure how mental health symptoms and conditions impact an individual's ability to perform in a work environment. Higher scores indicate better work-related functioning.

Health literacy will be measured with a visual analogue scale with the following question (translated from Spanish): "Please indicate your level of satisfaction with the information provided to you by the Catalan Institute of Oncology (ICO) regarding your illness and treatments, where 0 is very dissatisfied with the information received, and 10 is very satisfied with the information received ".

Intervention Satisfaction will be measured with a visual analogue scale with the following question (translated from Spanish): "Rate from 0 to 10 to what extent you are satisfied with the ICOnnecta't/ICognition Intervention, where 0 is completely dissatisfied and 10 is completely satisfied".

App Usability will be measured with a visual analogue scale with the following question (translated from Spanish): "Rate from 0 to 10 to what extent you found the application easy to use, where 0 is very difficult to use and 10 is very easy to use"

Institut d'Investigació Biomèdica de Bellvitge

Carlos III Health Institute

Institut Català d'Oncologia

PhD, Clinical Psychologist

Blood and Lymph Conditions

Hematologic Neoplasms

Hematologic Diseases

The arm will begin the Lumosity program at enrollment in the study.

The arm will begin the Lumosity program 3 months after enrollment in the study.

Computer-based online cognitive training program using the Lumosity cognitive training program.

Lumosity

Computer-based online cognitive training program using the Lumosity cognitive training program. The control group will receive the intervention after a waiting period of 12 weeks.

Lumosity (waitlist control)

Noha M Sharafeldin, MD,MSc, PhD

Lindsey Hageman, MPH

Noha Sharafeldin, MD, MSc, PhD

Lindsey Hageman, MPH, CCRP

Noha M Sharafeldin

A pilot study to evaluate feasibility of enrollment of patients in an intervention to improve neurocognitive function in hematopoietic cell transplantation (HCT) survivors using the cognitive training Lumosity program. In addition, patients' interest in receiving information regarding genetic risk of cognitive impairment post-HCT will be measured.

The investigators propose using an "off-the-shelf" product - Lumosity (http://www.lumosity.com/) - an online cognitive training program, to address the cognitive impairment in outpatient HCT survivors. The program offers over 60 tasks in game-like format that cover the main cognitive domains: processing speed, working memory, and executive function. Training will involve a daily session of 5 training tasks for 12 weeks. Each time the patient is logged in for a session, a customized report will be generated by the Lumosity program to capture performance information.

Ideally, targeting the intervention and offering it specifically to those at highest risk (integrating clinical and genetic markers) would ensure efficacy. However, evidence is lacking on whether patients are receptive to communication of individual genetic information and whether provision of such results would lead to enhanced intervention response. To realize the high expectations of personalized medicine, patients' preferences and attitudes need to be thoroughly investigated especially as more information on genetic risk becomes available. The investigators will examine patients' genetic knowledge to determine whether factual knowledge of genetics is essential for understanding genetic risk and for informing treatment decision making in this patient population.

Cognitive Training Intervention and Attitudes Towards Genetics

Intervention Strategies to Improve Cognitive Functioning in Hematologic Cancer Survivors After Hematopoietic Cell Transplantation

Number of participants completing the 12 week intervention

Change in cognitive function will be measured using cognitive test scores at baseline and 12 weeks

Genetic factual knowledge will be measured using a 16-item survey on knowledge about genes, chromosomes, cells, and diseases and how different characteristics are inherited from parents.

Effect size of associations of sociodemographic characteristics such as age, gender, race/ethnicity, education and income levels with genetic factual knowledge of participants will be measured.

Patient ratings will be collected on a 5 Likert scale survey questionnaire to examine importance of receiving information on genetic risk of cognitive impairment post-HCT.

Patient ratings will be collected on a 5 Likert scale survey questionnaire to measure association of likelihood of genetic risk of cognitive impairment (low chance vs high chance) on intervention uptake.

Patient ratings will be collected on a 5 Likert scale survey questionnaire to measure association of likelihood of genetic risk of cognitive impairment (low chance vs high chance) on intervention adherence.

University of Alabama at Birmingham

Prinicipal Investigator

Depressive Disorder

Depression

Behavioral Symptoms

Anti-Inflammatory Agents

All Drugs and Chemicals

Triamcinolone

Triamcinolone Acetonide

Triamcinolone hexacetonide

Triamcinolone diacetate

15 sessions of 20 minutes each one.Training will focus on the stimulation of several cognitive functions (attention, memory and learning, language, executive functions,processing speed, etc) through different exercises. The sessions will be adjusted to the individual performance level. The participant will perform these exercises from their computer or tablet, through the NeuronUp2GO platform, and the researcher will have access to all the session data.

tDCS: 15 daily sessions targeting left DLPFC (anode: F3, cathode: Fp2) Current intensity will be set at 2mA and will be applied for 20 minutes, with 15-second ramps up and down at the beginning and end of the stimulation period.

During the session, the participant will be performing the OCT.

tACS: 15 daily sessions targeting left DLPFC (anodes: F3, F4; frequency: 4Hz -theta-tACS-). Current intensity will be set at 2mA and will be applied for 20 minutes, with 15-second ramps up and down at the beginning and end of the stimulation period.

Participant will be performing the OCT during stimulation.

15 sessions of sham stimulation for 20 minutes, acting as a placebo control group. The electrode montage will be the same as that used in the active neuromodulation conditions: tDCS for half of the participants and tACS for the other half. In this sham stimulation condition, the current will only be delivered for a 15 seconds, at the ramp-up and ramp-down times at the beginning and end of the session.

The OCT will also be the same as those performed by participants in the other groups

Transcranial Direct Current Stimulation

Transcranial Alternating Current Stimulation

tES sham

Online Cognitive Training

María Teresa Carrillo de la Peña

Cristina Salgado Blanco

María Teresa Carrillo de la Peña, PhD

María Teresa Carrillo de la Peña, PhD, University teacher

Diego Pinal Fernández, PhD, University teacher

Cristina Salgado Blanco, PhD Student

Noelia Samartín Veiga, Postdoc

Alberto González Villar, Postdoc

Lara Rubal Otero, PhD Student

Carlos Spuch Calvar

The goal of this clinical trial is to test a home-delivered intervention that combines Non-Invasive Brain Stimulation techniques (transcranial direct and alternating current stimulation -tDCS and tACS-) and Online Cognitive Training (OCT) to treat depressive symptomatology and cognitive decline associated with breast cancer. The main questions aims to be answered are:

* To analyze the efficacy and feasibility of the intervention to treat depressive symptomatology.
* To analyze the efficacy and feasibility of the intervention to treat cognitive decline.
* To evaluate the medium and long-term effects (1, 3 and 6 months) of intervention.

An OCT program and a portable wireless tDCS/tACS system will be used to perform the intervention at home. Patients will be divided into four treatment groups, depending on whether they will receive the OCT applied independently or combined with tDCS/tACS active or sham.

In addition, saliva samples will be collected to identify bomarkers predictive of treatment efficacy.

This study is aimed at analyzing the feasibility and therapeutic efficacy of a home-based treatment using tDCS/tACS and an OCT program to treat depressive symptomatology (primary outcome variable) associated with breast cancer.The effect of the intervention on the patients' cognitive functioning (secondary outcome variable) will be also studied. In addition, saliva biomarkers and other clinical variables will be analyzed to determine whether they are related to the response to treatment. Finally, the impact of the intervention on the burden of the relatives/caregivers will be studied.

Oncology Units of the Galician Health Service will be contacted for recruitment. Oncologists will review whether patients meet the inclusion criteria and none of the exclusion criteria. If so, patients will be given an information flyer and will contact the research team to receive more information and, if they wish, to participate in the study. If patients are interested in participating, researchers will contact them to confirm the inclusion/exclusion criteria and participants will be invited to the first face-to-face session. In this session, informed consent will be signed, pre-treatment neuropsychological assessment will be performed, medical data will be reviewed, and a saliva sample will be collected. After collecting this data, the first treatment session will take place in the presence of the researcher. The type of treatment each patient will receive (OCT, tDCS active+ OCT, tACS active+ OCT or sham neurostimulation+ OCT. ) will be chosen randomly, using a randomization list.

After that, each patient will undergo 14 sessions, daily, at home. The tES devices (Soterix Medical Inc) have been designed for home use and allow the application of the stimulation by the patient himself, while being monitored by the researcher. The OCT will be delivered through NeuronUp2GO platform.Possible adverse effects associated with neurostimulation (which are mild and transitory) and other variables that may affect its efficacy (medication diary, caffeine intake...) will be monitored daily.

Finally, a post-treatment assessment will be carried out 15 days after the start of treatment and a follow-up assessment will be carried out 1, 3 and 6 months after the end of treatment. The 15-day and 1 month assessments will be the same as the pre-treatment (questionnaries and neuropsychological test). The follow-ups at 3 and 6 months will be done online, by filling in questionnaires.

Both the treatment administration and analysis of the results will be blinded.

First, descriptive analyses will be performed on the sociodemographic and clinical data. To evaluate the efficacy of the treatments on depressive symptomatology and subjective cognitive complaints, ANOVAs will be calculated under classical and Bayesian statistical frameworks, with Group (4 arms) as inter-participant factor and Time (pre, post, 1, 3 and 6 months follow-up) as intra-participant factor, following an Intention-to-Treat approach (including possible missing data after randomization). ANOVAs will also be calculalted with with Group (4 arms) as inter-participant factor and Time (pre, post, 1 month follow-up) as intra-participant factor to calculate the efficacy of the treatments on neuropsychological indexes. The possible modulating effect of sociodemograpchic and clinical variables on treatment efficacy will be analyzed. Also, for the clinical validation of the treatments, the analysis of the Minimal Clinically Important Difference (MCID) at short (15 days), medium (1 month) and long term (3 and 6 months) will be included. The difference between the pre- and post-treatment assessment in the primary and secondary variable scores should be equal to or greater than 30%.

Proteomic analysis will be performed at the Fundación Biomédica Galicia Sur. The following analysis will be performed: determination of total protein, mass spectrometry and electrophoretic separation of the samples by SDS-PAGE and identification of the bands of interest by Shotgun. The whole sample will be analyzed in liquid mass spectrometer (LC-MS/MS). Linear or logistic regression analysis will be performed to determine the predictive power of the saliva biomarkerson treatment efficacy.

Since the present research involves adult humans, it will be conducted under applicable international, EU and national laws and regulations (The Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects; The International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) Guidelines; the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine; and the UNESCO Universal Declaration on Bioethics and Human Rights (2005). Permission has been obtained from the local IRB committee (CEIm de Galicia) to conduct the study.

In terms of data protection, this study complies with the directives of the General Data Protection Regulation (GDPR), approved by the European Commission on April 27, 2016 (EU 2016/679) and with the Organic Law 3/2018, of December 5, 2018, on the Protection of Personal Data and guarantees of digital rights. The storage and treatment of the samples will be carried out in accordance with the Biomedical Research Law 14/2007 and RD 1716/201.

Patients' clinical data will be collected in the study-specific data collection notebook using REDCap (Research Electronic Data Capture), a secure web-based application for building and managing online surveys and databases. Data collection will be pseudo-anonymous, protecting the identity of the participant. Only the principal investigator of the entity responsible for data collection (USC) will know the pseudonymization codes. The research team will have access to all coded data collected for the study.

Randomized, four-arm, placebo-controlled, parallel-structured, double-blinded clinical trial.

In this study, a double-blind design will be used, since the device used for the tDCS/tACS intervention allows for total blinding. The patient and the researchers involved in treatment will be blinded to the group of treatment (except for the OCT group). Evaluation and data analysis will be blinded to group assignment until the participant has completed the study. Only the members of the research team in charge of generating the randomization list will have access to the patient's intervention status.

Non-Invasive Brain Stimulation and Cognitive Training for Depressive Symptomatology Related to Breast Cancer (ONCODEP)

Intervention With Non-Invasive Brain Stimulation and Cognitive Training for Depressive Symptomatology Associated With Breast Cancer (ONCODEP)

To assess the verbal span and working memory with series of digits in increasing and decreasing order (5 minutes).

To examine recent and delayed verbal learning and memory delayed (30 minutes,including the delay between trials).

To assess lexical and semantic fluency and executive components of language (5 minutes).

To examine perceptual comparison and processing speed (3 minutes).

Evaluate the response cost of performing a task individually or while performing it simultaneously. The tasks consist of recalling a series of digits in direct order and letter and symbol cancellation tasks.(5 minutes).

To assess examines selective attention and concentration using a cancellation task (10 minutes)

To assess anxious symptomatology (7 items, scored on a Likert scale from 0 to 3). Scores range between 0 and 21, with higher scores indicating higher anxious symptomatology.

To examine presence of fatigue symptoms (7 items, scored on a Likert scale from 1 to 5). Scores range between 7 and 35, with lower scores indicating higher fatigue symptoms.

The QLQ-C30 is composed of both multi-item scales and single-item measures. The questionnaire icludes five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status / QoL scale, and a number of single items assessing additional symptoms commonly reported by cancer patients.

All of the scales and single-item measures range in score from 0 to 100.

A high scale score represents a higher response level:

* A high score for a functional scale represents a high / healthy level of functioning,
* A high score for the global health status / QoL represents a high QoL,
* A high score for a symptom scale / item represents a high level of symptomatology / problems.

To assess sleep quality and disturbances over a 1-month. The questionnaire includes 19 items, combined to form seven scales to evaluate different components of sleep (subjective quality, latency, duration, efficiency, disturbances, medication use, sleep dysfunction). Each scale obtain a score that ranges from 0 to 3 (0- no difficulty, 3- severe difficulty). The 7 components are summed to obtain an overall quality o sleep score, from 0 to 21 points (0 - no difficulty, 21 - severe difficulty).

To assess the burden (stress and negative feelings) associated with the caregiving task. It is composed of 22 items answered according to a Likert scale range from 0 to 4. The cut-off point for caregiver burden is 46-47.

It also makes a distinction between mild burden (up to 56) and heavy burden (more than 56).

It measures the change in pain intensity, interference and discomfort afeter the treatment. There are three scales (intensity, interference, discomfort), which score range from 1 (no pain, no interference, no discomfort) to 10 (unbearable pain, interferes greatly and very unpleasant). Lower scores indicate a lower presence of pain symptoms.

To analyze general and cognitive self-efficacy. 7 items scored on a Likert scale from 1 to 5. A higher score reflects greater confidence in achieving certain self-efficacy related goals.

To know the subjective perception of improvement after treatment in terms of cognitive functioning, mood, fatigue, quality of sleep and quality of life. Each question is answered on a scale from 1 (no improvement) to 10 (great improvement).

Screening of depressive symptoms in medical patients (7 items, scored on a Likert scale from 0 to 3). BDI-FS minimum and maximum values range from 0 to 21, with higher scores meaning more depressive symptomatology.

To assess subjective cognitive complaints in the last week (8 items, scored on a Likert scale from 1 to 5). Minimum and maximum values rang from 8 to 40. Lower scores mean more subjective cognitive complaints.

Cognitive impairment screening that explores attention, concentration, executive functions, memory, language, visual-constructive abilities, calculation and orientation (10 minutes). Minimum and maximum values range from 0 to 30. Lower scores mean better cognitive functioning, The cutoff point for Mild Cognitive Impairment is 26.

Fundacin Biomedica Galicia Sur

University of Santiago de Compostela

University Professor

Immune System Diseases

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

GMT will be administrated in a group-based format over 5 sessions (minimum three weeks between each session). Homework assignments between sessions are included. Following the fourth session, text messages reading "Stop!" (a key instruction in GMT) will be sent to all GMT participants every day to maximize adherence to training (approximately 12 per participant). Homework assignment will also include the logging of automatic thoughts and an examination of the relationship between situations, thoughts, and accompanying emotions.

The adults participating in the control condition will approximately one year from waitlist, be offered a psycho-educative training program, the BHW, in groups aimed at providing a better understanding of cognitive sequelae after treatment for childhood ALL. BHW will be administrated in a group-based format over 5 sessions (minimum three weeks between each session). Homework assignments between sessions are included. Homework assignments between sessions are included.

The manual comprises an introduction to GMT for the survivors of ALL, and a detailed session structure incorporating cognitive and behavioral tasks. The GMT program involves teaching the participants about goals, attention slips and how to manage these, how to review and prioritize goals (e.g., Stop, Think, Organize, Plan), and how to keep goals in mind (e.g., using analogies such as the mental blackboard). Each session will follow the same general format; namely, facility-delivered presentations, flipchart discussions, group activities and homework.

Goal Management Training (GMT)

BHW is a psycho-educative control condition, and is typically part of psycho-educative Acquired Brain Injury (ABI) rehabilitation programs, but adjusted for the ALL group of participants. The psycho-educative control condition BHW will be matched GMT for amount of training and therapist contact. Homework assignment and in-session tasks included readings, brain games, puzzles, and practical exercises such as logging sleep.

Brain Health Workshop (BHW)

Magne Arve Flaten, phd prof

Paul Georg Skogen

Survivors of childhood cancer are at risk for developing neurocognitive sequelae. Multiple meta-analyses demonstrate significant deficits in overall intellectual abilities, academic functioning and specific cognitive skills among survivors of childhood cancer treated with intrathecal chemotherapy only and/or cranial irradiation. Preventing neurocognitive deficits is therefore of great importance. Unfortunately, intervention studies for this group of survivors are scarce. The main aim of this randomized controlled trial is to determine the efficacy of Goal Management Training (GMT) as a group-based treatment program for 60 adult survivors of childhood leukemia, and non Hodgkins lymphoma, diagnosed between 1980 and 2017 at an age below 18, with attention and executive function deficits. The participants will be randomized to one treatment group (GMT), and one waitlist condition followed by one active control intervention, the "Brain health workshop" (BHW), which has a psycho-educative approach. The follow-up time from diagnosis will be ≥5 years and the age at survey 18-40 years. The study will expand the knowledge base on treatment factors important in improving cognitive function. Results from this study can be implemented in rehabilitation for the young adult survivors of childhood leukemia, and non Hodgkins lymphoma, which will be of importance for their future educational and work-related functioning.

Effect of the GMT/waitlist conditions will be assessed through self-reported and objective measures of neuropsychological function, quality of life and health measurements. To avoid extra training effects of neuropsychological testing on participants allocated to waitlist/BHW, assessment following BHW (approximately one-year post T1) will consist of self-report measures only. Patients in all groups will be reassessed within 14 days post intervention (T2), and at 6 months post intervention (T3).

Goal Management Training for Adult Survivors of Childhood Leukemia and Non-Hodgkins Lymphoma With Neurocognitive Sequelae

The Effect of Goal Management Training for Adult Survivors of Childhood Leukemia and Non-Hodgkins Lymphoma With Neurocognitive Sequelae: A Randomized Controlled Trial

The PedsQLTM4.0 is a measure of health-related quality of life. The 23-item PedsQL, version 4.0 Generic Core Scales, can be grouped into 4 domains of HRQOL: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). In addition to the four subscales, a Total Summary Health score (23 items) can be computed.

The HSCL-25 is a measure of mental health. The Hopkins Symptom Check List (HSCL-25) is a 25-item self-report measuring adult mental health symptoms within the previous week. Total sum scores range from zero (least symptomatic) to 100 (most symptomatic). A mean item score can also be calculated, in which 1,75 is a common clinical cut-off score. The HSCL-25 is a short version of the HSCL-90.

The GPSS is a measure of self-efficacy. The General Perceived Self-Efficacy Scale (GPSS) is a 10-item psychometric scale assessing the strength of an individual's beliefs in his/her ability to respond to controlled environmental demands and challenges. Items are rated on a 4-point Likert scale (1=not at all true to 4=exactly true). There is no cut-off score on this scale. However, the weighted variance equaled 25.91. Thus, a raw score of 24 is 1 SD below the weighted mean using T-norms from the German version.

The FSS is a measure of fatigue. The Fatigue Severity Scale (FSS) includes nine questions related to how fatigue interferes with certain activities; symptom severity is rated on a 7-point Likert scale (1=strongly disagree to 7=strongly agree). Based on previous reports on the prevalence of fatigue, an FSS score ≥5 is to be interpreted as indicative of severe fatigue.

The FQ is a measure of fatigue. The FQ is an 11-item questionnaire, assessing physical (items 1-7) and mental (items 8-11) symptoms of fatigue, along with a total score. All items are rated using a 4-point Likert scale (0 = better than usual, 1= no more than usual, 2 = much worse than usual. Fatigue "caseness" is defined by total dichotomized scores \>4 and a duration of ≥6 months.

The RSA includes 33 questions related to protective factors. Resilience is rated on a scale from 1 to 7, and a total score reflects degree of resilience. The higher the score on RSA scale, the more protective factors an individual is assumed to have, e.g., better psychological health, and thus, the individual seems to cope better with adverse life events. RSA consists of six factors divided into 1) intrapersonal resources ("Perception of self", "Planned future", "Social competence" and "Structured style"), and 2) interpersonal resources ("Family cohesion" and "Social resources").

The ESS is a measure of general level of daytime sleepiness. The measure includes 8 items, with scaled scores from 0 (would never doze) to 3 (high chance of dozing), participants are asked to rate their usual chances of dozing off or falling asleep in 8 different situations or activities- The reference range of "normal" ESS scores is zero to 10, while scores of 11-24 represent increasing levels of "excessive daytime sleepiness" (i.e., 0-5: Lower Normal Daytime Sleepiness, 6-10: Higher Normal Daytime Sleepiness, 11-12: Mild Excessive Daytime Sleepiness, 13-15: Moderate Excessive Daytime Sleepiness, 16-24: Severe Excessive Daytime Sleepiness). We will use ESS total score ≥13 as a clinical cut-off.

The ISI is a 7-item questionnaire is assessing the nature, severity, and impact of insomnia over the past month. A 5-point Likert scale (0 = none; 4 = very severe) is used to rate each item, with total scores ranging from 0-28 (Total score categories; 0-7; No clinical significant insomnia, 8-14: Subthreshold insomnia, 15-21: Clinical insomnia (moderate severity), 22-28 = Clinical insomnia (severe). We will use the ISI total score ≥15 as a clinical cut-off.

The PPI is part of the Patient Reported Outcomes Measurement Information System (PROMIS) and includes 8 items. Pain interference refers to the degree to which pain limits or interferes with the persons physical, mental, and social activities. Items range from 1 "not at all" to 5 "very much". An additional item asks the participant to rate average pain intensity for the last 7 days on another scale ranging from 1 "no pain" to 10 "worst pain imaginable".

The BPI consists of questions related to pain intensity and pain interference on function. Responses for each item ranges from 0 (no pain) to 10 (pain as bad as you can imagine). Pain severity score (sum score of intensity items 1 to 4) and interference score (sum score of interference items 5 to 10) are reported. In addition, one item measure the localization of the most intense pain.

The interview includes 32 items. Participants are asked about basic demographic information (e.g. years of education, occupation, living situation), medical conditions/ injuries (e.g. Have you ever been diagnosed with ADHD?), treatment/rehabilitation (e.g. Have you received cognitive rehabilitation?) and adverse life events (e.g. Have you lost a close family-member within the last 12 months?). In addition, participants are asked to describe challenges in their everyday life (e.g. Please tell me about challenges in your everyday life when it comes to achieving your goals, Do you easily get distracted from what you are doing?).

The BRIEF-A self-report questionnaire consists of 75 items on which the patient's symptoms are rated on a 3-point Likert scale. The questionnaire provides a Global Executive Composite (GEC) score (range 75-225) and two index scores: the Behavioral Regulation Index (BRI) (range 30-90) and the Metacognitive Index (MI) (range 40-120). Nine subscales are also provided: Inhibit (range 8-24), Shift (range 6-18), Emotional control (range 10-30), Self-monitor (range 6-18), Initiate (range 8-24), Working memory (range 8-24), Plan/organize (range 10-30), Task monitor (range 6-18) and Organization of materials (range 8-24). Higher scores indicate more executive difficulties. Raw scores are transformed into t scores (M=50, SD=10).

The CPT 3 is a measure of inattention, impulsivity, sustained attention and vigilance. The test is computer based and lasts approximately 14 minutes. The participant is instructed to press the space bar/computer mouse when letters appear, but not when Xs appear on the screen. Higher scores reflect worse performance, and raw scores are converted to T-scores (M=50, SD=10). However, scores will be recoded so that higher scores equal better performance/lower scores equal worse performance.

The CWI is a measure of inhibition and cognitive flexibility. The test consists of four conditions; color naming (condition 1), word reading (condition 2), inhibition (condition 3) and inhibition switching (condition 4). Scores are computed for completion time (condition 1-4) and total errors (condition 3 and 4). Higher scores reflect better performance, and raw scores are converted to scaled scores (M=10, SD=3).

The TMT from Delis Kaplan Executive Function System is a measure of flexibility/shifting. The primary measure is condition 4 where the participant is asked to shift between number and letter sequencing. The test also measures the basic abilities of visual scanning (condition 1), number- and letter sequencing combined with drawing a line (condition 2 and 3) and motor pace (Condition 5). Scores reflect completion time and raw scores are converted to scaled scores (M=10, SD=3). Higher scores reflect better performance.

The CVLT II a measure of verbal learning and memory. Participants are asked to recall words from list A, both with and without an interruption list B. There are three types of conditions; the participant is asked to freely recall items (free recall), to recall after a cue is presented (cued recall) and to recognize previously presented words (recognition condition). Both short and long delay is measured. Raw scores are converted to Z-scores (M=0, SD=1) and T-scores (M=50, SD=10). Higher scores reflect better performance, except for error measures. For T2 (14 days) follow up, CVLT II Alternative Form will be used.

The WCST-64 is a measure of abstract thinking and set-shifting/ mental flexibility. The participant is instructed to sort cards according to varying principles. A computer-based version will be employed. Raw scores are converted to T-scores (M=50, SD=10) and higher scores reflect better performance.

The Hotel Task is a measure of executive components: planning, organization, self-monitoring and cognitive flexibility. The participant is asked to try out as many as possible of five tasks within a relatively short (15 minutes) time period. Raw scores are computed. Higher scores reflect better performance, except for deviation of optimal time use. The test has been demonstrated to have high ecological validity and ability to detect frontal lobe dysfunction.

The DEX - self-report is a measure of everyday problems with executive function. The questionnaire consists of 20 items with a 5-point Likert scale where the respondent is asked to rate the frequency of cognitive difficulties from 0 (never) to 4 (very often). A higher total score reflects worse executive functioning.

The subtests: Digit span, letter-number sequencing performance will be used as a measure of Verbal working memory/attention (Working memory index).

St. Olavs Hospital

Oslo University Hospital

Norwegian Cancer Society

Norwegian University of Science and Technology

We will collect: 1) self-reported demographic information (\~5 min) 2) cognitive functioning data (PAOFI) at session 1 and session 4 (\~10min) \[60\]; 3) behavioral data and EEG data from the tDCS stimulation task for each session (downloaded by investigators); 4) patient feedback on their experience with tDCS (tDCS Patient Experience Questionnaire (tPEQ)) for each session (\~5 min); 5) tDCS accrual and session completion rates at the completion of treatment and 6) Brunoni Adverse Events Questionnaire (\~5 min)

Transcranial Direct Current Stimulation (tDCS)

Questionnaires

James Root, PhD

In this study, the investigators are testing transcranial direct current stimulation (tDCS) in breast cancer survivors. In this pilot study, the investigators want to learn if it is feasible to use this device in memory rehabilitation.

Feasibility and Tolerability of Transcranial Direct Current Stimulation With Concurrent Cognitive Training

Pilot Study of Feasibility and Tolerability of Transcranial Direct Current Stimulation With Concurrent Cognitive Training

feasibility defined by the number of subjects recruited in a six month time frame

Memorial Sloan Kettering Cancer Center

Participants will participate in computer-based cognitive training at the end of therapy.

At the end of therapy, participants will participate in the current standard-of-care which does not include computer-based cognitive training.

Cogmed is a computer-based cognitive training program that consists of rotating exercises that train attention and working memory. The exercises are presented in a child-friendly, game-like format. The program is completed at home for 15-45 minutes each weekday for 5-9 weeks.

Cognitive training

Lisa M. Jacola, PhD

Computer-based cognitive training has been found to be helpful for improving attention and working memory in pediatric and adult patients with existing cognitive difficulties. A previous study was conducted at St. Jude Children's Research Hospital with survivors of childhood cancer who were experiencing difficulties with attention and/or working memory. Findings from that study indicated that the use of Cogmed, computer-based cognitive training, is effective in improving attention and working memory in survivors.

Researchers want to learn whether Cogmed intervention completed at the end of therapy for acute lymphoblastic leukemia will be effective for all survivors (i.e., regardless of whether they have existing difficulties).

PRIMARY OBJECTIVES:

* To evaluate the overall participation rate in a randomized, standard-of-care controlled trial of computerized cognitive intervention administered at the end of TOTXVI therapy.
* To estimate the study completion rate in a randomized, standard-of-care controlled trial of computerized cognitive intervention administered at the end of TOTXVI therapy.
* To estimate the compliance rate for participants randomized to the intervention arm of a computerized cognitive intervention administered at the end of TOTXVI therapy.
* To estimate the standard deviation for the overall cohort on a measure of working memory.
* To use neuroimaging data collected in the context of the Total Therapy XVI trial to explore candidate biomarkers predictive of response to the computerized cognitive intervention.

Participants enrolled on the TOTXVI protocol at SJCRH will be randomized to either complete the Cogmed intervention at the end of their therapy, or to a standard-of-care condition.

Cogmed is a computer-based cognitive training program that consists of rotating exercises that train attention and working memory. The exercises are presented in a child-friendly, game-like format. Training is completed at home in 25 sessions for 15-45 minutes each weekday for 5-9 weeks. A research team member serves as a coach who monitors progress and provides support through weekly phone calls with study participants and their parents/guardians. Information regarding compliance and performance is tracked over the internet and used to tailor feedback during weekly telephone coaching.

Neurocognitive assessments will be conducted at baseline, immediate-post (3-4 months after baseline), and 8 month follow-up (12 months after baseline).

Participants will be randomized to either the intervention group to receive cognitive training or to the standard of care group who will not receive cognitive training.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
eHealth Interventions for Breast Cancer Cognitive Impairment	NCT06103318	Breast Cancer Cognitive Dysfu...	ICOgnition	18 Years - 65 Years	Institut Català d'Oncologia
Cognitive Training Intervention and Attitudes Towards Genetics	NCT03094026	Cognitive Impai... Hematologic Neo... Hematopoietic C...	Lumosity Lumosity (waitl...	21 Years -	University of Alabama at Birmingham
Non-Invasive Brain Stimulation and Cognitive Training for Depressive Symptomatology Related to Breast Cancer (ONCODEP)	NCT06053775	Depressive Symp... Cognitive Impai...	Transcranial Di... Transcranial Al... tES sham Online Cognitiv...	30 Years - 65 Years	University of Santiago de Compostela
Goal Management Training for Adult Survivors of Childhood Leukemia and Non-Hodgkins Lymphoma With Neurocognitive Sequelae	NCT04541056	Childhood Non-H... Childhood Acute... Childhood Acute...	Goal Management... Brain Health Wo...	18 Years - 40 Years	Norwegian University of Science and Technology
Feasibility and Tolerability of Transcranial Direct Current Stimulation With Concurrent Cognitive Training	NCT02726763	Breast Cancer S...	Transcranial Di... Questionnaires	40 Years - 65 Years	Memorial Sloan Kettering Cancer Center
Non-Invasive Brain Stimulation and Cognitive Training for Depressive Symptomatology Related to Breast Cancer (ONCODEP)	NCT06053775	Depressive Symp... Cognitive Impai...	Transcranial Di... Transcranial Al... tES sham Online Cognitiv...	30 Years - 65 Years	University of Santiago de Compostela
Cognitive Intervention at the End of Therapy for Survivors of Childhood ALL Treated on TOTXVI	NCT03187977	Acute Lymphobla...	Cognitive train...	4 Years -	St. Jude Children's Research Hospital
Cognitive Training in the Virtual Reality Setting With Children Undergoing Radiotherapy for Brain Tumors	NCT05947045	Brain Tumor	Cognitive train... Cognitive train...	8 Years - 22 Years	St. Jude Children's Research Hospital
Application of Cognitive Training Based on Remind Strategy in Glioma Patients With Cognitive Impairment	NCT06327048	Glioma	Individual cogn...	18 Years - 70 Years	LanZhou University

Spots Global Cancer Trial Database for cognitive training