Symptoms and General Pathology

All Conditions

Behaviors and Mental Disorders

Neoplasms

Skin and Connective Tissue Diseases

Nervous System Diseases

Rare Diseases

Pain, Postoperative

Anxiety Disorders

Breast Neoplasms

Chronic Pain

Pain

Breast Diseases

Skin Diseases

Neurologic Manifestations

Postoperative Complications

Quality of Life

Chronic Graft Versus Host Disease

Cognitive behavioural therapy (CBT) is a talking therapy that can help patients manage problems by changing the way they think and behave. It's most commonly used to treat anxiety, depression and chronic pain conditions.

Education and mindfulness therapy refers to lessons on techniques to calm the mind and body - can reduce the negative effects of stress

The CBT intervention will be delivered by a Senior Psychologist with seventeen years of hospital psychology experience, six in the treatment of chronic pain patients. Sessions are delivered in one hour, individual therapy appointments to patients, and there is an emphasis on relaxation training, cognitive restructuring, exercise and pacing, behavioral activation, improving sleep, and anger management. Standardized worksheets and homework assignments are an important part of CBT-CP and these will be given (post or email) to patients who will be asked to read and complete in terms of complementing the consultations. This intervention has been developed with reference to two sources: A successful national implementation of CBT for chronic pain (CBT-CP) using video teleconferencing format \[Connolly KS et al\] AND an evidence-based CBT manual specifically designed to treat chronic pain \[Murphy JL et al\].

Cognitive Behavioural Therapy (CBT)

To control for differences in attention between the two interventions, patients in the mindfulness group will also have two meetings before the surgery and two meetings afterward. As the same person will be providing the CBT-CP and educational interventions, this confounding factor will be controlled for. The control intervention consists of discussing pain education, as derived from the self-management section of the chronic pain Ireland website (https://www.chronicpain.ie/our-services/self-management) and the persistent pain section of the pain toolkit website (https://www.paintoolkit.org/persistent-pain). Four mindfulness-based stress reduction exercises will be completed including an introductory session on mindful breathing, a guided meditation, progressive muscle relaxation, and a body scan. These sessions will last about half an hour.

Education and Mindfulness

Donal Buggy, MB Bch BAO

Chronic persistent post-surgical pain (CPSP) is defined as pain at or near the site of surgery persisting for 3 months or more after the date of surgery. The incidence CPSP in Europe is up to 50% at 3 months and 12% at 12 months, but the incidence varies depending on surgical procedure \[Fletcher D et al\]. In Breast surgery, one of the most commonly performed surgical procedures for cancer \[Kehlet H et al\], CPSP has been observed in 20-30% of patients at 6 months after surgery, making this group among the highest risk of developing CPSP \[Spivey TL et al \& Weiser TG et al\]. Clinical developments that could mitigate the development of CPSP after breast cancer surgery would potentially yield multiple benefits in terms of reducing future healthcare utilization, associated costs \[Spivey Tl et al\], and improving their physical and mental health.

Several predictive factors for CPSP have been identified, the most important being chronic pre-operative pain, high intensity of acute postoperative pain, and several psychological factors \[Vranceanu A-M et al\]. Of these psychological factors, pain catastrophizing has emerged as one of the strongest predictors of pain severity and disability among individuals with a range of pain presentations and CPSP \[Leung L \& Wade Jb \& Wildeman TH\]. Catastrophizing is described as a maladaptive psychological coping strategy involving an exaggerated reaction to anticipated or actual pain. It can involve mental rumination, magnification of the perceived danger or threat associated with pain, and feelings of helplessness in relation to what can be done \[Leung L et al\]. A recent systematic review on psychological interventions undergoing major elective abdominal surgery concluded catastrophization can have a direct influence on the neuropathophysiological mechanisms underlying pain experiences and can improve pain and psychological outcomes, after surgery \[Villa G et al\].

In recent years, there has been a growing number of studies investigating the potential impact of perioperative psychological interventions in a variety of patient groups. A recent systematic review and meta-analysis of observational studies concluded that psychological predictors may have a significant association with chronic postsurgical pain, including catastrophization, although this conclusion is limited by the heterogeneity of study designs and methods used \[Giusti et al\]. To our knowledge, no randomized controlled trial has been done to date, investigating the influence of perioperative psychological interventions on CPSP in patients undergoing breast cancer surgery.

This will be a single-center, prospective, double-blinded, randomized controlled trial. The study will randomize breast cancer surgery patients into two groups: one that receives perioperative cognitive-behavioral therapy (CBT) in addition to usual care and the other receives an educational program. The estimated duration for the main investigational plan (e.g. from the start of screening of the first participant to the last participant processed and finishing the study) is one year.

Aims and objectives:

The primary objective is to examine whether a perioperative CBT-based psychological intervention is effective at reducing pain intensity at three-month follow-up, in high catastrophizing patients undergoing breast cancer surgery, compared to an education program.

Secondary objectives of the study include examining whether perioperative CBT has a demonstrable impact on patients, compared to a time-matched education program, with regard to additional self-reported secondary outcomes, including quality-of-recovery, pain catastrophizing, pain interference, depression, and anxiety.

Participants and recruitment:

Adult patients who are undergoing breast surgery (defined as wide excision with magseed surgery or full mastectomy patients with or without axillary clearance) who are proficient in the English language will be eligible for inclusion. Patients will be enrolled at the outpatient clinic of the Department of Anaesthesiology and the Breast Health Department at the Mater Misericordiae University Hospital. All patients entering the screening phase of the study will be registered on a Study Patient Registration Log and a unique registration number will be assigned. Clinical data will be assessed to evaluate a subject's eligibility.

Patients eligible for participation will be evaluated approximately two weeks before surgery and asked for informed consent, and then asked to complete the Pain Catastrophizing Scale (PCS) \[Sullivan M et al\] by a member of the research team. Patients with high pain catastrophizing, defined as a score of ≥24 on the PCS, will be eligible for randomization to perioperative treatment with CBT or the education and mindfulness program. This cut-off is based on a previous study that showed a pre-treatment score of 24 or higher on the PCS best-predicted follow-up chronic pain ratings and work status after multidisciplinary treatment\[Scott W et al\] and has since been selected as an appropriate score cut-off in a perioperative CBT intervention in lumbar surgery patients \[Scarone P et al\]. More recently, this cut-off was also suggested to obtain the highest sensitivity and specificity to predict unfavorable outcomes after spinal surgery \[Tuna T et al\].

Randomization:

Patients will be randomized after they are included in the study, having consented and completed the PCS (and scoring scored ≥24), and two preoperative appointments will be scheduled with the patients in the intervention and control groups. Patients will be randomized to either 'CBT' or 'Education' group by using an online computer-generated block randomization. The patient study number and group allocation will be typed onto separate pages and concealed in sequentially numbered sealed envelopes. Block randomization will occur as follows; 12 subjects per block to ensure even numbers of participants in each arm of the study and the number of blocks that will be used is 4. Randomization will be performed by an independent third party. The randomization key/seed will also be held by an independent third party and investigators will not have access to this key/seed until the study has been completed.

The envelope will be opened by the treating psychologist to reveal the group allocation. Patients and members of the research team involved in data collection and analyzing the data will be masked to group allocation. The treating psychologist will not be blinded. Group allocations will be revealed immediately if there was a clinical concern.

All patients in both interventional arms:

All patients, irrespective of group allocation, will be routinely prescribed medications for pain control and will be referred for physical therapy on an out-patient basis, or other services, depending on clinical indications and personal needs.

Sample size, power considerations, and statistical analysis:

The primary outcome is the difference in the BPI average pain severity score and average pain interference score between the study groups, three months after surgery. A clinically important difference on the BPI is a 2 raw score reduction on the 11-point NRS \[Wong K et al \& Marcus J et al \& Mease PJ etl al\]. The standard deviation (SD) of BPI scores after breast surgery is in the order of 2.3 on this scale (Burckhardt CS et al). Taking a BPI score reduction of 2 as being clinically significant, then n=21 patients would be required each arm if Type I error=0.05 and Type II error is 0.2 (power 80%). Taking into account a 10% drop-outs rate, we propose to enroll 24 eligible patients in each group (N=48 total).

Baseline patient characteristics will be stratified by group and presented as mean and standard deviation (SD), median and first and third quartile, and count and percentage, as appropriate. Differences in baseline characteristics between randomized groups will not be statistically tested, whereas differences with the separate control cohort will be tested using the independent-samples t-test for continuous variables, and Pearson's chi-square test for categorical variables. In case of expected cell counts of less than 5, Fisher's Exact test will be used instead.

All patients randomized (i.e. those with a PCS score \> 24) will be analyzed in an intention-to-treat analysis. To test for a difference between the CBT and control group in the BPI 'average' pain intensity scale at three months, linear regression will be used. Adjustment for the type of surgery, age, and education will be made and, if necessary, for other prognostic variables significantly associated with the outcome (i.e., acute postoperative pain intensity, the severity of catastrophizing, preoperative depression, preoperative surgical fear, length of current sick leave, pain duration).

Secondary outcome variables will be analyzed similarly to the primary outcome. For these, logistic regression analysis will be used to test for differences in proportions at three months postoperatively. For exploratory purposes, we will compare the outcomes of the patients in the two intervention groups with the outcomes of patients with low pain catastrophizing scores (i.e. those with a PCS score \< 24) undergoing care as usual. Linear mixed-effects regression for the three groups will be performed with primary and secondary outcomes at the three postoperative assessment periods and controlling for preoperative values. This analysis will indicate whether high catastrophizing patients follow a similar trajectory of pain and functioning after breast surgery compared to non-catastrophizing patients.

Patients will be blinded to which intervention they will receive. The outcome assessors for this study will be unaware as to which group the participant will be randomised to and therefore they will be blinded to which intervention the participant had received

Effect of Perioperative CBT on Chronic Persistent Postsurgical Pain Among Breast Cancer Patients

Effect of Perioperative Cognitive Behavioural Therapy on Chronic Persistent Postsurgical Pain Among Breast Cancer Patients With High Pain Catastrophising Characteristics: A Randomised, Double-blind Clinical Trial

Individual Patient Data sharing will be supported with qualified external researchers and supporting clinical documents from eligible studies. All data provided will be coded and anonymised to respect the privacy of patients who have participated in the trial

BPI Short-form is a 9 item questionnaire used to evaluate the severity of a patient's cancer or non cancer pain \[Tan G et al\]. Brief Pain Inventory short-form scale is measured between 0 - 10, where '0' indicates no pain and '10' indicates severe pain. A decrease in the Brief Pain Inventory score of 2 or more from the baseline score is considered significant and indicates an improvement in severity of the patient's cancer and non-cancer pain.

QoR-15 is a 15-item questionnaire which is used as a tool to assess overall patient recovery and pain after surgery. Participant will be asked to complete this questionnaire within24-48 hours after their surgery. It is scored between 0 and 150, where the greater the number indicates excellent post-operative recovery. \[Chazapis M et al\].

PCS is a 13-item questionnaire designed to measure levels of pain-catastrophizing. The scale comprises 13 items which yield an overall catastrophizing score, which is a composite of magnification, rumination, and helplessness subscales \[Sullivan M et al\]. A Pain Catastrophizing score of greater than 24 is significant for increased risk of developing chronic pain.

HADS is a 14 item self reported questionnaire that was developed and found to be a reliable method for detecting states of depression and anxiety in the setting of a hospital medical outpatient clinic \[Zigmond AS et al\]. The score scale ranges between 0-21. A score between 0-7 is normal, a score between 8-10 is considered borderline abnormal and a score between 11-21 is abnormal and indicates a high likelihood that the patient is suffering from anxiety and or depression.

BPI Short-form is a 9 item questionnaire used to evaluate the interference the pain has on his/her daily functioning \[Tan G et al\]. BPI is measured between 0 - 10, where '0' indicates no interference and '10' indicates severe interference with quality of life.

Mater Misericordiae University Hospital

Research Fellow in Anaesthesia and Perioperative Medicine

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Central Nervous System Stimulants

Nicotine

Nicotinic Agonists

Cholinergic Agents

Neurotransmitter Agents

Patients enrolled in group 1 will receive a Nicotine Replacement Therapy (NRT) from the study entry to end of study

Patients enrolled in group 2 will receive a Nicotine Replacement Therapy (NRT) from the study entry to end of study and 1 to 3 Motivational Interviewing (MI) after randomization

Patients enrolled in group 3 will receive a Nicotine Replacement Therapy (NRT) from the study entry to end of study and 1 to 3 Motivational Interviewing (MI) after randomization and 6 sessions of CBT after Motivational Interviewing up to 6 months after

Patients enrolled in group 4 will receive a Nicotine Replacement Therapy (NRT) from the study entry to end of study and 1 to 3 Motivational Interviewing (MI) after randomization and about 3 sessions of hypnotherapy up to 6 months after

1 to 3 Motivational Interviewing (MI) should be performed after randomization by a psychotherapist

Motivational Interviewing (MI)

6 Cognitive Behavioural Therapy (CBT) sessions should be performed after motivational interviewing up to 6 months by a psychotherapist

About 3 Hypnotherapy sessions should be performed after motivational interviewing up to 6 months by a hypnotherapist

Hypnotherapy

All patients will receive Nicotine Replacement Therapy (NRT) from randomization up to 6 months

Nicotine Replacement Therapy (NRT)

This trial offers support and assistance to patients wishing to quit smoking in order to increase the success rate of smoking cessation and all the benefits associated with it. Patients will be monitored by a tobacco specialist and will be able to benefit from one or more therapies complementary to Nicotine Replacement Therapy (NRT): Motivational Interviewing (MI), Cognitive Behavioural Therapy (CBT) or Hypnotherapy.

The study RESPIRE is aiming to identify some interventions to be proposed as part of a smoking cessation programme for smokers with cancer requiring surgical treatment and wishing to stop smoking. We aim to compare different smoking cessation methods in addition to the currently recommended treatments: Nicotine Replacement Therapy (NRT). These procedures are: Cognitive Behavioural Therapy (CBT), Motivational Interviewing (MI) or hypnotherapy in order to improve the success rate of smoking cessation in this specific population.

All patients wishing to be supported to stop smoking will be randomized and will be followed by a tobacco specialist before and after surgery. They will receive NRT for 12 months.

Smoking assessment, exhaled CO measurement, questionnaires will be completed regularly to assess depression, anxiety and quality of life during the 12 months.

Patients randomized in group 2 will receive 1 to 3 MI. Patients randomized in group 3 will receive 1 to 3 MI and 6 CBT sessions by a psychotherapist.

Patients randomized in group 4 will receive 1 to 3 MI and at least 3 sessions oh hypnotherapy.

pilot study, monocentric, prospective, randomization according to Zelen's design

Evaluation of Different Smoking Cessation Protocols: Nicotine Replacement, Motivational Interviewing (MI), Cognitive Behavioural Therapy (CBT) or Hypnotherapy in Cancer Patients Scheduled for Surgery

Pilot Study in Cancer Patients Scheduled for Surgery Evaluating Different Smoking Cessation Protocols : Nicotine Replacement, Motivational Interviewing (MI), Cognitive Behavioural Therapy (CBT) or Hypnotherapy

Number of patients who completed all planned sessions out of the total number of patients randomised to each group

Percentage of patients with an exhaled Carbone Monoxide (CO) measurement \< 10 ppm at study visits.

Percentage of patients reporting no smoking during the last 7 days before the visit.

Number of cigarettes smoked per day from baseline

Percentage of patients reporting no smoking since surgery

Report all Grade \> 1 side effects of oncology treatments up to 3 months after the end of treatment or the end of the study

Report all surgical complications (Grade \> 1 according to Clavien Dindo classification) up to 1 month after surgery

Patient Depression and anxiety will be evaluated by using the Hospital Anxiety and Depression Scale (HADS)

Patient quality of life will be evaluated by using the Quality of Life Questionnaire (QLQ-C30)

National Cancer Institute, France

Institut Cancerologie de l'Ouest

Digestive System Diseases

Musculoskeletal Diseases

Heart and Blood Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Syndrome

Neoplasm Metastasis

Irritable Bowel Syndrome

Fibromyalgia

Myofascial Pain Syndromes

Tachycardia

Chest Pain

Cough

Hyperventilation

Postural Orthostatic Tachycardia Syndrome

Neoplastic Processes

Cognitive behavioural therapy + Standard Medical Care (cognitive-behavioural therapy+SMC):

8 hour-long manual-based CBT sessions with a therapist, weekly or fortnightly.

Participants assigned to the SMC group (i.e., control group) will receive all the treatment and support they would otherwise receive outside of a research trial.

Behavioral: Cognitive behavioural therapy (CBT) The CBT intervention used in the trial has been adapted for people with PPS and it is based on a model of understanding PPS (Deary et al 2007). The therapy aims to help the patient develop an understanding of the relationship between cognitive, physiological and behavioural aspects of their problem; to understand factors that may be maintaining the problem and to learn how to modify their behavioural and cognitive responses in order to improve quality of life. The approach is transdiagnostic in that it targets processes and underlying mechanisms that affect disorders similarly, rather than focusing on how they are diagnostically different. The approach is personalised during therapy following a detailed assessment.

Cognitive behavioural therapy (CBT)

Trudie Chalder, PhD

Brief Summary: Persistent Physical Symptoms (PPS), also known as medically unexplained symptoms (MUS) is a term used to describe a range of persistent bodily symptoms for which the exact cause is unclear. Between 20 and 40% of patients in primary care, and about 50% in secondary care experience PPS. Not only are PPS common, but the overlap across different patient groups may indicate that these phenomena are transdiagnostic. PPS are associated with profound disability and high health care costs, and if left untreated the prognosis of these patients is poor. There is an accumulating body of evidence demonstrating that cognitive behavioural interventions can reduce levels of symptoms and improve functioning in patients with PPS. A pragmatic randomised controlled trial (RCT) was designed to evaluate the clinical and cost-effectiveness of cognitive behavioural therapy (CBT) + Standard Medical Care (SMC) versus Standard Medical Care alone, in the treatment of patients with PPS. The trial will focus on patients with a variety of symptoms (e.g., non-cardiac chest pain, fibromyalgia), across secondary care clinics (e.g., neurology, cardiology, and rheumatology).

Background and study aims In primary care between 20 and 40% of patients have medically unexplained physical symptoms. The term medically unexplained symptoms (MUS) is commonly used by health care professionals. However a survey of a healthy population and a separate survey of patients with chronic fatigue syndrome (CFS) suggested that the term persistent physical symptoms (PPS) was the preferred term. The term PPS may have its drawbacks, but it will be used in the rest of this document to cover MUS as well as any other terms that may be used in the literature and clinical settings to refer to these symptoms. In secondary care, about 50% of patients have PPS, in many specialties. PPS are associated with profound disability and high health care costs. Around 50% of sufferers have co-morbid anxiety and depression and sleep problems. Left untreated, the prognosis of these patients is poor.

This study is a pragmatic RCT that will evaluate the clinical and cost-effectiveness of cognitive behavioural therapy + standard medical care (CBT+SMC), which involves 8 sessions of CBT, versus standard medical care (SMC) in the treatment of patients with PPS.

Who can participate? Patients with various PPS, such as fibromyalgia, non-cardiac chest pain, irritable bowel syndrome and a range of neurological symptoms e.g., weakness will be recruited. Participants will be recruited from clinics in secondary care (e.g., neurology, cardiology, rheumatology) at various hospitals in London.

What does the study involve? Potential participants will be identified by clinical staff who will refer them to the research team. Patients who give their consent to take part in the study will complete a number of questionnaires asking about their symptoms and use of health care services, and about their thoughts, feelings, and beliefs related to their PPS (i.e., baseline). This will take approximately 1.5 hours. After this research assessment, half of participants will be randomly assigned to the treatment arm (CBT+SMC), or to the control (SMC) arm. Participants in the treatment arm will receive 8 individual sessions of CBT (weekly or fortnightly sessions). The therapy aims to help the patient develop an understanding of the relationship between cognitive, physiological and behavioural aspects of their problem; to understand factors that may be maintaining the problem and to learn how to modify their behavioural and cognitive responses in order to improve their quality of life. Participants in the SMC group will receive usual medical care within the clinic.

Participants in both arms will also be asked to complete questionnaires at 9, 20, 40, and 52 weeks after randomisation. The assessment will be independent of the health care professionals delivering care.

What are the possible benefits and risks of participating? By taking part in the study patients may get helpful information about their condition. If assigned to the CBT+SMC arm, patients will receive 8 sessions of CBT focused on helping them manage their symptoms, which may improve their symptoms and increase their psychosocial functioning. It is unclear whether CBT for patients with PPS is effective; this trial will assess whether there are benefits to receiving it. Patients may benefit from being followed up closely and completing measures. It is not expected that participation in the study is associated with risks. The therapists involved in the trial are highly qualified specialists with extensive experience in treating patients with PPS. The trial team also includes a psychiatrist who will further ensure patient safety in complex cases. Participants will be free to take a break at any point during the meetings and are free to withdraw from the study at any point. Participants will also be informed that they can raise any concerns they may have with the research team and will be provided with the Patient Advice \& Liaison Service contact information.

Where is the study run from? The study has been set up by the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King's College London and the South London and Maudsley National Health Service (NHS) Foundation Trust, and will be conducted at several hospitals in London/Greater London, including Guy's and St Thomas' Hospitals, King's College Hospital, Princess Royal University Hospital, Royal Free Hospital, University Hospital Lewisham and Queen Elizabeth Hospital.

When is the study starting and how long is it expected to run for? The study has started in July 2015 and the end date for the project is March 2019.

Who is funding the study? The study is funded by the Guy's and St. Thomas' Charity.

Who is the main contact? Prof Trudie Chalder trudie.chalder@kcl.ac.uk

CBT Plus SMC Compared to SMC for Persistent Physical Symptoms in Secondary Care (PRINCE)

The PRINCE Secondary Study: Persistent Physical Symptoms Reduction Intervention: a System Change and Evaluation in Secondary Care

Measures improvement of patient-defined self-rated problems

Measures severity, distress, interference and problematic nature of PPS

Measures patient's perception of their general health improvement

Measures health care service receipt, direct and indirect costs of illness, and cost-effectiveness of interventions

assesses degree of acceptance of difficult symptoms

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Perioperative CBT on Chronic Persistent Postsurgical Pain Among Breast Cancer Patients	NCT04924010	Breast Cancer Chronic Pain Chronic Postsur... Quality of Life	Cognitive Behav... Education and M...	18 Years - 75 Years	Mater Misericordiae University Hospital
Evaluation of Different Smoking Cessation Protocols: Nicotine Replacement, Motivational Interviewing (MI), Cognitive Behavioural Therapy (CBT) or Hypnotherapy in Cancer Patients Scheduled for Surgery	NCT04899492	Breast Cancer Gynecologic Can... Digestive Cance... Melanoma	Motivational In... Cognitive Behav... Hypnotherapy Nicotine Replac...	18 Years -	Institut Cancerologie de l'Ouest
CBT Plus SMC Compared to SMC for Persistent Physical Symptoms in Secondary Care (PRINCE)	NCT02426788	Persistent Phys...	Cognitive behav...	18 Years - 70 Years	King's College London

Spots Global Cancer Trial Database for cognitive behavioural therapy (cbt)