NCT06727773

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

Type	Name	Description
DRUG	Memantine	memantine capsule
DRUG	Placebo medication	placebo 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	Exercise Control	Exercise control will have access to a library of pre-recorded Get Real \& Heel sessions.

Timeline

• Start date: 2025-05-07
• Primary completion: 2028-10-31
• Completion: 2028-10-31
• First posted: 2024-12-11
• Last updated: 2025-09-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study