Clinical trial NCT06727773: Memantine and Exercise to Improve Cognitive Function and Modulate Biological Pathways of Cognitive Decline During Chemotherapy in Breast Cancer
Official title: Memantine and Exercise to Improve Cognitive Function and Modulate Biological Pathways of Cognitive Decline During Chemotherapy in Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2024-12-11
Enrollment: 90
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rates of recruitment
timeFrame: Baseline
measure: Rates of retention
timeFrame: Up to a year
measure: Rates of adherence
timeFrame: Up to a year
measure: The acceptability of memantine + Get Real and Heel (MEM+EX)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Attention and Executive Function Composite Score
timeFrame: Baseline and up to 1 year
measure: Learning and Memory Composite Score
timeFrame: Baseline and up to 1 year
measure: Changes in patient-reported cognition
timeFrame: Baseline and up to 1 year
measure: The impact of MEM+EX and memantine on brain-derived neurotrophic factor (BDNF)
timeFrame: Baseline and up to 6 months
measure: The impact of MEM+EX and memantine on inflammatory markers
timeFrame: Baseline and up to 6 months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Zev Nakamura, MD
role: PRINCIPAL_INVESTIGATOR
References: