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NCT Number: NCT06727773

Memantine and Exercise to Improve Cognitive Function and Modulate Biological Pathways of Cognitive Decline During Chemotherapy in Breast Cancer

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.

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Key information

Conditions

Breast Cancer Behavior Breast Cancer Stage I Breast Cancer Stage II Breast Cancer Stage III Breast Diseases Breast Neoplasms Cognition Disorders Cognitive Change Cognitive Decline Cognitive Dysfunction Cognitive Impairment Locally Advanced Breast Cancer Mental Disorders Motor Activity Neoplasms Neoplasms by Site Neurocognitive Disorders Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location status: Recruiting

Location contact

Zev M Nakamura, MD

CONTACT

[email protected]

Zev M Nakamura, MD

PRINCIPAL_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

In order to participate in the study a subject must meet all of the eligibility criteria outlined below.

  • Female
  • Age ≥ 18 years at the time of consent.
  • Stage I-III Breast Cancer
  • Recommended chemotherapy
  • Enroll prior to 3rd cycle of chemotherapy
  • English-speaking

Exclusion criteria

  • 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
  • Cardiovascular or orthopedic limitations to exercise
  • Severe mental illness (i.e., schizophrenia or bipolar affective disorder)
  • Current alcohol or drug abuse
  • Inability to swallow capsules </= 5mL/min
  • CrCl </= 5mL/min

Treatment and study plan

Memantine

Drug

memantine capsule

Placebo medication

Drug

placebo capsule

Exercise intervention

Other

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.

Other names: Get Real & Heel

Exercise Control

Other

Exercise control will have access to a library of pre-recorded Get Real & Heel sessions.

Other names: Exercise library

Primary outcomes

  1. Rates of recruitment

    Time frame: Baseline

    Rates of recruitment will be measured as a number of subjects joined the study.

  2. Rates of retention

    Time frame: Up to a year

    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

  3. Rates of adherence

    Time frame: Up to a year

    Rates of adherence will be measured as a number of subjects who joined the study completed 80 percent of planned study activities.

  4. The acceptability of memantine + Get Real and Heel (MEM+EX)

    Time frame: Up to 6 months

    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).

Secondary outcomes

  1. Attention and Executive Function Composite Score

    Time frame: Baseline and up to 1 year

    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.

  2. Learning and Memory Composite Score

    Time frame: Baseline and up to 1 year

    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.

  3. Changes in patient-reported cognition

    Time frame: Baseline and up to 1 year

    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.

  4. The impact of MEM+EX and memantine on brain-derived neurotrophic factor (BDNF)

    Time frame: Baseline and up to 6 months

    The impact of MEM+EX and memantine on putative biomarkers of CRCI will be determined by examining changes in BDNF compared to placebo.

  5. The impact of MEM+EX and memantine on inflammatory markers

    Time frame: Baseline and up to 6 months

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Ashley M Hanson

CONTACT

[email protected]

+1 984-888-9244

Sponsors and collaborators

Lead sponsor

UNC Lineberger Comprehensive Cancer Center

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
Dec 11, 2024
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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