Memantine and Exercise to Improve Cognitive Function and Modulate Biological Pathways of Cognitive Decline During Chemotherapy in Breast Cancer
Purpose
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.
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
Eligibility
- Eligible Ages
- Over 50 Years
- Eligible Genders
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
In order to participate in this study a subject must meet all of the eligibility criteria outlined below. - Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information. The subject is willing and able to comply with study procedures based on the judgment of the investigator. - Female - Age ≥ 50 years at the time of consent. - Stage I-III Breast Cancer - 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
Exclusion Criteria
- Allergy to memantine - Previous radiation, cancer-directed hormonal therapy, chemotherapy (prior to the current regimen), or immune checkpoint inhibitors - Severe cognitive impairment, defined by Blessed Orientation Memory Concentration Test Score ≥11 - >30 min vigorous or >60 min moderate physical activity per week - 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 Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- 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.
- Primary Purpose
- Supportive Care
- Masking
- Triple (Participant, Care Provider, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm 1 |
Participants will receive study medication (memantine) and Get Real & Heel exercise guided by the therapist. |
|
|
Placebo Comparator Arm 2 |
Participants have access to a library of pre-recorded Get Real & Heel sessions. |
|
|
Experimental Arm 3 |
Participants will receive study medication (memantine) and access to a library of pre-recorded Get Real & Heel sessions. |
|
Recruiting Locations
Chapel Hill, North Carolina 27599
More Details
- NCT ID
- NCT06727773
- Status
- Recruiting
- Sponsor
- UNC Lineberger Comprehensive Cancer Center
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.