This randomized, placebo-controlled trial aims to assess the feasibility, acceptability, and preliminary efficacy of memantine and the University of Carolina (UNC)'s Get Real \& Heel cancer exercise program (MEM+EX) in addressing cancer-related cognitive impairment (CRCI) and underlying CRCI biomarkers. Ninety stage I-III breast cancer patients during chemotherapy will be randomized into three groups: MEM+EX, memantine, or placebo. The study will evaluate recruitment, retention, adherence, acceptability, cognitive function, brain-derived neurotrophic factor (BDNF), inflammatory markers, and frailty at multiple time points.
Female
Age ≥ 18 years at the time of consent.
Stage I-III Breast Cancer
Recommended chemotherapy
Allergy to memantine
Previous chemotherapy (prior to the current regimen),
Severe cognitive impairment, defined by Blessed Orientation Memory Concentration Test Score ≥11
Myocardial infarction in the last 6 months
Parallel
Memantine
Drugmemantine capsule
Placebo medication
Drugplacebo capsule
Exercise Intervention
Other interventionExercise Intervention participants will concurrently engage in remotely delivered Get Real \& Heel, 3d/week. Intensity for aerobic and strength-training components will progress as tolerated under the direction of a trained exercise physiologist.
Exercise Control
Other interventionExercise control will have access to a library of pre-recorded Get Real \& Heel sessions.
Rates of recruitment
Rates of recruitment will be measured as a number of subjects joined the study.
Rates of retention
Rates of retention will be measured as the proportion of subjects who remained in the study at post-intervention (up to 6 months) and after 6 months among those who started the intervention
Rates of adherence
Rates of adherence will be measured as a number of subjects who joined the study completed 80 percent of planned study activities.
The acceptability of memantine + Get Real and Heel (MEM+EX)
The acceptability of memantine + Get Real and Heel (MEM+EX) will be assessed using the Client Satisfaction Questionnaire (CSQ-3). CSQ-3 is a three-item measure of treatment acceptability that has demonstrated excellent reliability and validity across a range of patient care settings. Each item is scored on a Likert-type scale from 1 (low satisfaction) to 4 (high satisfaction). CSQ-3 will be completed at post-intervention only (or at the time of withdrawal from the study, if applicable).
Attention and Executive Function Composite Score
The attention and executive function score is a composite of the following neuropsychological assessment measures: Digit Span, Trail Making Test Parts A\&B, Controlled Oral Word Association Test, and Animal Naming Test. It will be calculated as the sum of Z-scores (standardized based on available age-, sex-, education-, and race/ethnicity-matched normative data) of the individual subtests and range from a Z-score of -3 to +3.
Learning and Memory Composite Score
The learning and memory score is a composite of the following neuropsychological assessment measures: Hopkins Verbal Learning Test-Revised and Brief Visual Memory Test-Revised. It will be calculated as the sum of Z-scores (standardized based on available age-, sex-, education-, and race/ethnicity-matched normative data) of the individual subtests and range from a Z-score of -3 to +3.
Changes in patient-reported cognition
The impact of MEM+EX and memantine on cognitive function will be determined by examining changes in patient-reported cognition, as measured by the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog PCI) version 3, compared to placebo. FACT-Cog PCI is a self-report measure designed to assess perceived cognitive functioning in cancer patients, particularly those experiencing chemotherapy-induced cognitive problems. It consists of 18 items and each item is rated on a 5-point Likert scale, ranging from 0 (Never) to 4 (Several times a day). The total score is obtained by summing the subscale scores. Higher scores indicate better perceived cognitive functioning.
The impact of MEM+EX and memantine on brain-derived neurotrophic factor (BDNF)
The impact of MEM+EX and memantine on putative biomarkers of CRCI will be determined by examining changes in BDNF compared to placebo.
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UNC Lineberger Comprehensive Cancer Center
Lead sponsor
National Institute on Aging (NIA)
Collaborator
