A Phase 2 interventional study of Memantine and Placebo medication in Breast Cancer, Locally Advanced Breast Cancer and Cognitive Impairment, sponsored by UNC Lineberger Comprehensive Cancer Center. Recruiting at 1 site in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-06.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 2, Interventional, and Supportive care
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.
There are 4 million breast cancer survivors in the U.S. and an estimated 1.4 million suffer from long-term cognitive deficits from cancer treatment. Compared to other cancers and treatments, cognitive decline has been most robustly described in breast cancer and following chemotherapy with up to 75% self-reporting and \~50% objectively demonstrating at least mild cognitive deficits after chemotherapy. Memantine, an N-methyl-D-aspartate receptor antagonist, is a promising medication to address underlying mechanisms of CRCI, including inflammation and pathways involving brain-derived neurotrophic factor (BDNF). Exercise, a promising intervention for frailty which intervenes on multiple mechanisms of aging, is an ideal strategy to augment the targeted effects of memantine.
The primary objective of this study is to demonstrate the feasibility and acceptability of MEM+EX during breast cancer chemotherapy. Secondarily, the preliminary efficacy of MEM+EX and memantine on putative biomarkers of CRCI and cognitive function will be evaluated. Furthermore, the impact of frailty on the preliminary efficacy of MEM+EX and memantine will be explored.
The proposed study has the potential to produce significant public health benefit by filling a major gap in effective CRCI treatments. It will provide important pilot data for future, definitive randomized controlled studies. Finally, this study will advance understanding of potential targets to pursue in future cognitive interventions, including pathways involving BDNF and inflammation, during treatment for cancer.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's planned enrollment of 90 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →UNC Lineberger Comprehensive Cancer Center is the lead sponsor of 414 studies on the registry; 96 are open to participants now.
Of its 32 completed or terminated interventional studies of FDA-regulated products, 25 (78%) have results posted.
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In order to participate in the study a subject must meet all of the eligibility criteria outlined below.
Exclusion Criteria:
Participants will receive study medication (memantine) and Get Real \& Heel exercise guided by the therapist.
Drug: Memantine · Other: Exercise Intervention
Participants have access to a library of pre-recorded Get Real \& Heel sessions.
Drug: Placebo medication · Other: Exercise Control
Participants will receive study medication (memantine) and access to a library of pre-recorded Get Real \& Heel sessions.
Drug: Memantine · Other: Exercise Control
memantine capsule
placebo capsule
Exercise 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.
Also known as: Get Real & Heel
Exercise control will have access to a library of pre-recorded Get Real \& Heel sessions.
Also known as: Exercise library
Rates of recruitment
Rates of recruitment will be measured as a number of subjects joined the study.
Time frame: Baseline
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
Time frame: Up to a year
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.
Time frame: Up to a year
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).
Time frame: Up to 6 months
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.
Time frame: Baseline and up to 1 year
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.
Time frame: Baseline and up to 1 year
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.
Time frame: Baseline and up to 1 year
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.
Time frame: Baseline and up to 6 months
The impact of MEM+EX and memantine on inflammatory markers
The impact of MEM+EX and memantine on putative biomarkers of CRCI will be determined by examining changes in inflammatory composite measure (TNF-alpha, IL-6, CRP) compared to placebo.
Time frame: Baseline and up to 6 months
Plan to share: No
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UNC Lineberger Comprehensive Cancer Center