Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Behaviors and Mental Disorders

Breast Neoplasms

Cognitive Dysfunction

Breast Diseases

Skin Diseases

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Patients attend 3 weekly exercise sessions in weeks 1-2, 2 sessions each week in weeks 3-4, 1 session each week in weeks 5-8, biweekly sessions across weeks 9-16, and monthly sessions in weeks 17-24 for a total of 20 supervised sessions. Patients undergo MRI and wear an accelerometer throughout the study.

Patients participate in up to 9 monthly classes/webinars. Patients also receive informational pdfs, videos, and/or podcasts, and a one-year subscription to the Mayo Clinic Health Letter. Patients undergo a gait assessment and MRI, as well as wear an accelerometer throughout the study.

Breast cancer survivors in the intervention group will participate in a 24-week moderate intensity exercise program led by community-based fitness center personal trainers. Individually-tailored exercise prescriptions will be developed based upon each participant's baseline maximal graded exercise test (heart rate corresponding with %VO2 peak) and symptom limitation. Sessions will be progressive in nature such that the volume of exercise increases across weeks. Treadmill walking is the primary mode of exercise. However, participants will be permitted to use other cardiovascular equipment (e.g., elliptical machines, stationary bicycles) as prescribed by their exercise trainer. The trainer will supervise three weekly exercise sessions in Weeks 1-2, two in Weeks 3-4, one in Weeks 5-8, biweekly across weeks 9-16, and monthly in Weeks 17-24 (N=20 supervised sessions).

Aerobic Exercise Training

Breast cancer survivors in the Health Education group will participate in education sessions with a health educator and receive monthly newsletters/webinars (N=20 total contacts) across 24 weeks. The program will include cancer support and discussion of cancer-related wellness topics (e.g., stress management, coping). Control group participants will be offered a 6-month fitness center membership upon study completion.

Health Education (Active comparator)

Magnetic Resonance Imaging

Medical Device Usage and Evaluation

Gait Assessment

Gabriella Hickman, MS

Clinical Trials Referral Office

Diane K. Ehlers, Ph.D.

This phase II trial tests whether an exercise intervention works to improve cognitive function in breast cancer survivors. Many breast cancer survivors report cancer-related cognitive impairment, which this has recently become a priority in clinical research due to its dramatic impact on daily functioning, quality of life, and long-term health. Aerobic exercise has the potential to improve cognitive function and brain health in older adults and is recommended as a safe, tolerable, and accessible complementary therapy for breast cancer survivors. This study aims to understand the effects of physical activity compared with health education on memory, attention, and brain health in women with breast cancer. Study findings may help researchers design more programs that can improve memory, attention, and brain health in other women with breast cancer.

PRIMARY OBJECTIVES:

I. Examine the effectiveness of a 6-month, community-based aerobic exercise intervention on multiple indicators of cognitive function in post-menopausal breast cancer survivors.

II. Gather information on the intervention's potential for scalability using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework.

EXPLORATORY OBJECTIVE:

I. Explore potential moderators and mediators of the effects of aerobic exercise training on cognitive function.

II. Investigate the feasibility of urinary metabolites as biomarkers of overall diet patterns.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients attend 3 weekly exercise sessions in weeks 1-2, 2 sessions each week in weeks 3-4, 1 session each week in weeks 5-8, biweekly sessions across weeks 9-16, and monthly sessions in weeks 17-24 for a total of 20 supervised sessions. Patients undergo a gait assessment and magnetic resonance imaging (MRI), as well as wear an accelerometer throughout the study.

ARM II: Patients participate in up to 9 monthly classes/webinars. Patients also receive informational portable document format (pdfs), videos, and/or podcasts, and a one-year subscription to the Mayo Clinic Health Letter. Patients undergo a gait assessment and MRI, as well as wear an accelerometer throughout the study.

After completion of study intervention, patients are followed up with at 12 months.

Breast Cancer, Reasoning, and Activity Intervention

Enhancing Cognitive Function in Breast Cancer Survivors Through Community-based Exercise Training

Although the final dataset will not include identifying information, there is still a possibility of deductive disclosure of identity. Therefore, data will not be shared via an NIH or approved public repository; however, we will share de-identified data as required for publication in scientific journals and with outside collaborators and scientists upon request.

Change in interference score on Stroop task, with negative values indicating lower inhibitory control.

Change in reaction time on Task-switch task, with higher values indicating lower cognitive flexibility

Change in completion time on Trails B task, with higher values indicating lower executive function.

Change in reaction time on spatial working memory task, with faster reaction times indicating better spatial working memory

Change in accuracy on N-Back task, with higher accuracy indicating better short-term memory

Change in number recalled on Auditory Verbal Learning task, with greater number of items recalled indicating better verbal memory

change in response time, with shorter response time associated with faster relational memory processes

Change in accuracy on Flanker task, with greater accuracy indicating better working memory

change in mean cortical thickness of brain regions of interest as measured by an anatomic MRI brain scan

change in fractional anisotropy as measured by diffusion MRI.

change in within-network pairwise correlation estimates as measured using a multiband echo planar imaging (mb-EPI) functional MRI sequence

The perceived cognitive impairments subscale of the Functional Assessment in Cancer Therapy - Cognition (FACT-Cog) will be used to measure self-reported cognition. Scores range from 0-72, with higher scores indicating better cognitive function.

Participation rate among eligible individuals contacted about the study.

sociodemographics questionnaire to describe demographics characteristics and experience among personal trainers

Change in Peak VO2 as measured by a modified Balke treadmill graded exercise test protocol.

The Functional Assessment in Chronic Illness Therapy (FACIT) - Fatigue Scale will be used to measure cancer-related fatigue. Scores range from 0-52, with higher scores indicating less cancer-related fatigue.

percent of session checklist items completed as intended

The number of participants who withdraw during the follow-up period.

National Cancer Institute (NCI)

Mayo Clinic

Principal Investigator

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Musculoskeletal Diseases

Nervous System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Syndrome

Xeroderma Pigmentosum

Cockayne Syndrome

Trichothiodystrophy Syndromes

Ichthyosis

DNA Repair-Deficiency Disorders

Congenital Abnormalities

Skin Abnormalities

Infant, Newborn, Diseases

Keratosis, Actinic

Keratosis

Precancerous Conditions

Skin Diseases, Genetic

Genetic Diseases, Inborn

Photosensitivity Disorders

Pigmentation Disorders

Metabolic Diseases

Dwarfism

Bone Diseases

Bone Diseases, Developmental

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Abnormalities, Multiple

Trichothiodystrophy

Patients who are diagnosed with a DNA Repair Disorder

Healthy family members of enrolled diagnosed participants.

The study coordinator or another team member will review standard health questions relevant to DNA repair disorders. The control group will not undergo an interval history. These questions will include:

1. How the participant's appetite and general weight trajectory has been since the last assessment
2. Any episodes of unexplained bleeding or bruising
3. Any jaundice
4. General level of alertness and interaction with family and others
5. Any changes in cognitive function such as speech, following commands, comprehension
6. Any changes in motor function, including the development of tremors and stiffness in movements

Interval History

A board-certified neurologist (the principal investigator) will perform a general physical examination and a neurological examination and complete a standard CRF to document relevant findings. The control group will not undergo a physical examination.

Physical Examination

An Early Clinical Assessment of Balance (ECAB) will be performed by the physical therapist. Part I can be assessed in all affected individuals, and Part II requires ambulation. For non-ambulatory individuals, only Part I will be applied. The items in the ECAB are summarized as follows:

Part I. Head and trunk postural control (maximum 36 points) Head righting - lateral (right and left) Head righting - extension Head righting - flexion Rotation in trunk (right and left) Equilibrium reactions in sitting (right and left) Protective extension - side Protection extension - backward Part II. Sitting and standing postural control (maximum 64 points) Sitting with back unsupported but feet supported on floor or on a stool Sitting to standing Standing unsupported with eyes closed Standing unsupported with feet together Turns 360 degrees Placing alternate foot on the step while standing unsupported

ECAB Assessment

For ambulatory participants, the physical therapist will also assess standardized gait outcome measures, including:

1. Gait Speed: may be measured over a 10 meter distance, assessing both "comfortable" walking speed and "fast" walking speed
2. 10-meter walk/run: timed assessment at fastest gait attainable. This assessment would be omitted for those participants who are determined to have a high fall risk.
3. Timed Up and Go (TUG): time to stand from a chair, walk 3 meters, go around a cone, and return to the chair (with or without an assistive device)
4. Dynamic Gait Index (DGI): assesses 8 balance challenges while walking

Total blood volumes collected at each visit will be limited to 5mL/kg body weight, with a maximum of 18mL.

Saliva samples may be obtained if research is taking place where blood samples cannot be drawn or transferred.

Specimen Sample Collection

Erin Aguero

Peter Kang, MD

Natalya Alassy, MBS

This will be a single-center, single-arm, non-interventional natural history study to evaluate the longitudinal clinical course, functional outcome measures, and candidate biomarkers for individuals with DNA repair disorders, including Cockayne syndrome (CS), xeroderma pigmentosum (XP), and trichothiodystrophy (TTD).

This will be a single-center, single-arm, non-interventional natural history study to evaluate the longitudinal clinical course, functional outcome measures, and candidate biomarkers for individuals with DNA repair disorders, including Cockayne syndrome (CS), xeroderma pigmentosum (XP), and trichothiodystrophy (TTD). Our hypothesis is that a reliable and reproducible baseline natural history course can be established for DNA repair disorders using the Early Childhood Assessment of Balance (ECAB) as a primary endpoint and other measures as secondary and exploratory endpoints that may be used in future therapeutic clinical trials.

1. Comprehensive metabolic panel (CMP) that includes electrolytes, ALT, AST, and LDH.
2. GGT
3. Bilirubin
4. Complete blood count (CBC)
5. Neurofilament light (NfL)40-42
6. Glial fibrillary acidic protein (GFAP)43
7. Total tau (t-tau)44
8. Ubiquitin C-terminal hydrolase (UCHL1)45

Natural History Study for DNA Repair Disorders

This study will be conducted in accordance with the following publication and data sharing policies and regulations: National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for publication.

This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.

We have selected the following 4 biomarkers to be measured in serum samples at each study visit:

1. Neurofilament light (NfL)
2. Glial fibrillary acidic protein (GFAP)
3. Total tau (t-tau)
4. Ubiquitin C-terminal hydrolase (UCHL1)

We have selected the following 4 biomarkers to be measured in serum samples at each study visit:

1. Neurofilament light (NfL)40-42
2. Glial fibrillary acidic protein (GFAP)43
3. Total tau (t-tau)44
4. Ubiquitin C-terminal hydrolase (UCHL1)45 To determine whether a serum biomarker can track disease status and progression and serve as a secondary outcome measure. To determine genetic diagnoses for those who are genetically undiagnosed, and to use transcriptomic analyses to seek additional biomarker candidates.

The longitudinal stability of cerebellar and gait function will be assessed by the presence or absence of tremors (absence = 1, presence = 0), dysmetria (absence = 1, presence = 0), dysdiadochokinesia (absence = 1, presence = 0) and Gowers sign (absence = 1, presence = 0). The scores will be added to yield a total score ranging from 0 to 4, with 4 representing the best performance.

Longitudinal stability of motor function in study participants as assessed by gait speed measured over a 10 meter distance

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Breast Cancer, Reasoning, and Activity Intervention	NCT04816006	Breast Cancer Breast Neoplasm... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Cancer-related ...	Aerobic Exercis... Health Educatio... Magnetic Resona... Medical Device ... Gait Assessment	18 Years -	Mayo Clinic
Breast Cancer, Reasoning, and Activity Intervention	NCT04816006	Breast Cancer Breast Neoplasm... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Cancer-related ...	Aerobic Exercis... Health Educatio... Magnetic Resona... Medical Device ... Gait Assessment	18 Years -	Mayo Clinic
Natural History Study for DNA Repair Disorders	NCT05484570	DNA Repair Diso... Cockayne Syndro... Xeroderma Pigme... Trichothiodystr...	Interval Histor... Physical Examin... ECAB Assessment Gait Assessment Specimen Sample...	6 Months -	University of Minnesota

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