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

NCT06727773 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: LCCC2425K23AG086604
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer; Locally Advanced Breast Cancer; Cognitive Impairment; Cognitive Decline; Cognitive Change; Breast Cancer Stage I; Breast Cancer Stage II; Breast Cancer Stage III

Keywords

chemotherapy; memantine; placebo-controlled; exercise; Get Real & Heel cancer exercise program

Outcome Measures

Primary Outcomes (4)

• Rates of recruitment

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

  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

  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.

  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).

  Up to 6 months

Secondary Outcomes (5)

• Attention and Executive Function Composite Score

  Baseline and up to 1 year

• Learning and Memory Composite Score

  Baseline and up to 1 year

• Changes in patient-reported cognition

  Baseline and up to 1 year

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

  Baseline and up to 6 months

• The impact of MEM+EX and memantine on inflammatory markers

  Baseline and up to 6 months

Study Arms (3)

Arm 1

EXPERIMENTAL

Participants will receive study medication (memantine) and Get Real \& Heel exercise guided by the therapist.

Drug: Memantine; Other: Exercise Intervention

Arm 2

PLACEBO COMPARATOR

Participants have access to a library of pre-recorded Get Real \& Heel sessions.

Drug: Placebo medication; Other: Exercise Control

Arm 3

EXPERIMENTAL

Participants will receive study medication (memantine) and access to a library of pre-recorded Get Real \& Heel sessions.

Drug: Memantine; Other: Exercise Control

Interventions

Memantine DRUG

memantine capsule

Arm 1; Arm 3

Placebo medication DRUG

placebo capsule

Arm 2

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.

Also known as: Get Real & Heel

Arm 1

Exercise Control OTHER

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

Also known as: Exercise library

Arm 2; Arm 3

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

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

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Cognitive Dysfunction; Motor Activity

Interventions

Memantine; lime

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Zev Nakamura, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashley M Hanson

CONTACT

+1 984-888-9244; Ashley_Hanson@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to MEM+EX (memantine + exercise), memantine, or placebo using a computer-generated randomization scheme that stratifies for an equal balance of age. All study personnel and participants will remain blinded until data collection is complete.

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: December 11, 2024
• Study Start: August 19, 2025
• Primary Completion (Estimated): June 15, 2029
• Study Completion (Estimated): June 15, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)