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Clinical Trial NCT06727773 for Breast Cancer, Locally Advanced Breast Cancer, Cognitive Impairment, Cognitive Decline, Cognitive Change, Breast Cancer Stage I, Breast Cancer Stage II, Breast Cancer Stage III is recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here.
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Memantine and Exercise to Improve Cognitive Function and Modulate Biological Pathways of Cognitive Decline During Chemotherapy in Breast Cancer

Recruiting
Clinical Trial NCT06727773 is designed to study Supportive Care for Breast Cancer, Locally Advanced Breast Cancer, Cognitive Impairment, Cognitive Decline, Cognitive Change, Breast Cancer Stage I, Breast Cancer Stage II, Breast Cancer Stage III. It is a Phase 2 interventional trial that is recruiting, having started on May 7, 2025, with plans to enroll 90 participants. Led by UNC Lineberger Comprehensive Cancer Center, it is expected to complete by October 31, 2028. The latest data from ClinicalTrials.gov was last updated on September 2, 2025.
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 with mild cognitive difficulties 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.
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.

Official Title

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

Conditions
Breast CancerLocally Advanced Breast CancerCognitive ImpairmentCognitive DeclineCognitive ChangeBreast Cancer Stage IBreast Cancer Stage IIBreast Cancer Stage III
Other Study IDs
NCT ID Number
NCT06727773
Start Date (Actual)
2025-05-07
Last Update Posted
2025-09-02
Completion Date (Estimated)
2028-10-31
Enrollment (Estimated)
90
Study Type
Interventional
PHASE
Phase 2
Status
Recruiting
Keywords
chemotherapy
memantine
placebo-controlled
exercise
Get Real & Heel cancer exercise program
Primary Purpose
Supportive Care
Design Allocation
Randomized
Interventional Model
Parallel
Masking
Triple
Arms / Interventions
Participant Group/ArmIntervention/Treatment
ExperimentalArm 1
Participants will receive study medication (memantine) and Get Real \& Heel exercise guided by the therapist.
Memantine
memantine capsule
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.
Placebo ComparatorArm 2
Participants have access to a library of pre-recorded Get Real \& Heel sessions.
Placebo Medication
placebo capsule
Exercise Control
Exercise control will have access to a library of pre-recorded Get Real \& Heel sessions.
ExperimentalArm 3
Participants will receive study medication (memantine) and access to a library of pre-recorded Get Real \& Heel sessions.
Memantine
memantine capsule
Exercise Control
Exercise control will have access to a library of pre-recorded Get Real \& Heel sessions.
Primary Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
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 Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
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.
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.
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.
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.
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.
Baseline and up to 6 months
Eligibility Criteria

Eligible Ages
Adult, Older Adult
Minimum Age
18 Years
Eligible Sexes
Female

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

  • Female
  • Age ≥ 50 years at the time of consent.
  • Stage I-III Breast Cancer
  • Recommended chemotherapy
  • Enroll prior to 3rd cycle of chemotherapy
  • Completed at least 1 cycle of standard-of-care neoadjuvant or adjuvant chemotherapy
  • At least mild self-reported cognitive concerns ≥3 on a 0-10 scale
  • English-speaking

  • 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
UNC Lineberger Comprehensive Cancer Center logoUNC Lineberger Comprehensive Cancer Center
National Institute on Aging (NIA) logoNational Institute on Aging (NIA)
Study Central Contact
Contact: Ashley M Hanson, +1 984-888-9244, [email protected]
1 Study Locations in 1 Countries

North Carolina

Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, 27599, United States
Zev M Nakamura, MD, Contact, [email protected]
Zev M Nakamura, MD, Principal Investigator
Recruiting