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

May 1, 2026 updated by: UNC Lineberger Comprehensive Cancer Center
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill
        • Contact:
        • Principal Investigator:
          • Zev M Nakamura, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Participants will receive study medication (memantine) and Get Real & Heel exercise guided by the therapist.
Drug: Memantine
memantine capsule
Other: Exercise Intervention
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
Placebo Comparator: Arm 2
Participants have access to a library of pre-recorded Get Real & Heel sessions.
Other: Exercise Control
Exercise control will have access to a library of pre-recorded Get Real & Heel sessions.
Other Names:
  • Exercise library
Drug: Placebo medication
placebo capsule
Experimental: Arm 3
Participants will receive study medication (memantine) and access to a library of pre-recorded Get Real & Heel sessions.
Drug: Memantine
memantine capsule
Other: Exercise Control
Exercise control will have access to a library of pre-recorded Get Real & Heel sessions.
Other Names:
  • Exercise library

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of recruitment
Time Frame: Baseline
Rates of recruitment will be measured as a number of subjects joined the study.
Baseline
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
Up to a year
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.
Up to a year
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).
Up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and up to 6 months
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.
Baseline and up to 6 months
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.
Baseline and up to 1 year
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.
Baseline and up to 1 year
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.
Baseline and up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Zev Nakamura, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 19, 2025

Primary Completion (Estimated)

June 15, 2029

Study Completion (Estimated)

June 15, 2029

Study Registration Dates

First Submitted

November 22, 2024

First Submitted That Met QC Criteria

December 5, 2024

First Posted (Actual)

December 11, 2024

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LCCC2425
  • K23AG086604 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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