Memantine + Exercise for Cognitive Impairment in Breast Cancer

Overseen By Ashley M Hanson

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Severe cognitive impairment, Severe mental illness, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment Memantine + Exercise for Cognitive Impairment in Breast Cancer?

Research shows that increasing physical activity can improve cognitive functioning in healthy and cognitively impaired adults, and exercise has shown positive effects on cognitive function in breast cancer survivors. Although Memantine is not specifically mentioned in these studies, exercise alone has been identified as a promising strategy to support cognitive health in cancer patients. ^{1 2 3 4 5}

Is memantine safe for humans?

Memantine has been shown to be generally safe and well-tolerated in clinical trials for Alzheimer's disease, with side effects like headache, diarrhea, and dizziness being the most common. The safety profile of memantine is comparable to placebo, meaning it does not cause more adverse events than a sugar pill in studies. ^{6 7 8 9 10}

How does the treatment of memantine and exercise differ for cognitive impairment in breast cancer patients?

This treatment is unique because it combines memantine, a drug that helps protect brain cells and is used in Alzheimer's disease, with exercise to potentially improve cognitive function in breast cancer patients undergoing chemotherapy. There is currently no standard treatment for cognitive difficulties in these patients, making this approach novel. ^{6 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

Zev Nakamura, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for stage I-III breast cancer patients experiencing mild cognitive difficulties during chemotherapy. Participants must be willing to be randomly placed into one of three groups and be assessed at multiple points for cognitive function and other health markers.

Inclusion Criteria

My breast cancer is at an early to mid-stage (I-III).

Written informed consent obtained to participate in the study and HIPAA authorization for the release of personal health information

I am 50 years old or older.

Exclusion Criteria

Severe mental illness (i.e., schizophrenia or bipolar affective disorder), Current alcohol or drug abuse

Allergy to memantine

Severe cognitive impairment, defined by Blessed Orientation Memory Concentration Test Score ≥11

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive memantine and participate in the Get Real & Heel exercise program during chemotherapy

6 months

Regular visits as per chemotherapy schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Periodic assessments

Long-term follow-up

Participants are assessed for long-term cognitive function and biomarker changes

Up to 1 year

Treatment Details

Interventions

• Exercise
• Memantine

Trial Overview The trial is testing the combination of a drug called Memantine and a specific exercise program (MEM+EX) against Memantine alone and a placebo. The goal is to see if these interventions can improve cognitive function and biological markers related to cognitive decline.

Participant Groups

Group I: Arm 3 Experimental Treatment 2 Interventions

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

Group II: Arm 1 Experimental Treatment 2 Interventions

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

Group III: Arm 2 Placebo Group 3 Interventions

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

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

This study will evaluate the impact of a 3-month physical activity intervention on cognitive functioning in 80 sedentary breast cancer survivors who report cognitive difficulties, comparing results to a waitlist control group.

The research aims to uncover not only changes in neuropsychological outcomes and cognitive concerns but also the biological mechanisms behind these effects by analyzing biomarkers related to brain health and physical activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of increasing physical activity on cognitive functioning in breast cancer survivors: Rationale and study design of Memory & Motion. Hartman, SJ., Natarajan, L., Palmer, BW., et al.[2022]

The EPICC Study is a randomized controlled trial involving 254 postmenopausal women with early-stage breast cancer, testing the impact of a six-month moderate-intensity aerobic exercise program on cognitive function during aromatase inhibitor therapy.

This study aims to address cognitive impairment, which affects up to 75% of breast cancer survivors, and if successful, could establish exercise as a low-cost, adaptable intervention to improve cognitive health in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy. Gentry, AL., Erickson, KI., Sereika, SM., et al.[2023]

Memantine is an uncompetitive NMDA receptor antagonist that helps reduce glutamatergic excitotoxicity, showing modest improvement in clinical symptoms and potentially slowing disease progression in moderate-to-severe Alzheimer's disease and other forms of dementia.

Unlike cholinesterase inhibitors, which only provide symptomatic relief, memantine has been effective in severe stages of dementia and is the first drug to completely eliminate pendular nystagmus in multiple sclerosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine: pharmacological properties and clinical uses. Kumar, S.[2013]

In a study involving 30 patients aged 55 to 84 with moderate to severe Alzheimer's disease, memantal (a generic form of memantine) demonstrated moderate positive effects on cognitive functions and daily activities over a 3-month treatment period.

The treatment was found to be safe, with no adverse effects reported, indicating that memantal is both effective and well-tolerated for managing symptoms of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of the use of memantal in patients with moderate and severe Alzheimer's disease]. Gavrilova, SI., Kolykhalov, IV., Kulik, AS., et al.[2018]

Memantine is an NMDA receptor antagonist that has shown neuroprotective and cognition-enhancing effects in animal models, and it has been clinically effective in improving cognitive performance in patients with Alzheimer's disease and vascular dementia.

Clinical trials have demonstrated that memantine is well-tolerated, with a low incidence of adverse events, making it a safe option for treating moderately severe to severe Alzheimer's disease, leading to its approval in both Europe and the US.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine hydrochloride: pharmacological and clinical profile. Möbius, HJ., Stöffler, A., Graham, SM.[2017]

Memantine is a unique NMDA receptor antagonist that selectively blocks harmful glutamate activity associated with Alzheimer's disease while preserving normal cognitive function, making it a promising treatment option.

Clinical studies have shown that memantine improves symptoms and slows clinical deterioration in patients with moderate-to-severe Alzheimer's disease, leading to its approval in the US in 2003.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of memantine for the treatment of Alzheimer's disease. Ferris, SH.[2019]

Whole brain radiation therapy, the primary treatment for brain metastases in low to middle income countries, is linked to irreversible cognitive decline.

Memantine has been shown to help reduce the rate of cognitive decline and delay cognitive failure in cancer patients undergoing whole brain radiotherapy, suggesting it may be a beneficial therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic role of memantine for the prevention of cognitive decline in cancer patients with brain metastasis receiving whole-brain radiotherapy: a narrative review. Folloso, MC., Torres, M., Ciocon, SL., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Impact of increasing physical activity on cognitive functioning in breast cancer survivors: Rationale and study design of Memory & Motion. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Impact of aerobic exercise training during chemotherapy on cancer related cognitive impairments in patients suffering from acute myeloid leukemia or myelodysplastic syndrome - Study protocol of a randomized placebo-controlled trial. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Effect of physical exercise on cognitive function and brain measures after chemotherapy in patients with breast cancer (PAM study): protocol of a randomised controlled trial. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Associations Between Physical Fitness Indices and Working Memory in Breast Cancer Survivors and Age-Matched Controls. [2022]

6. India pubmed.ncbi.nlm.nih.gov

Memantine: pharmacological properties and clinical uses. [2013]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical experience of the use of memantal in patients with moderate and severe Alzheimer's disease]. [2018]

8. Spain pubmed.ncbi.nlm.nih.gov

Memantine hydrochloride: pharmacological and clinical profile. [2017]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Memantine extended release (28 mg once daily): a review of its use in Alzheimer's disease. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Evaluation of memantine for the treatment of Alzheimer's disease. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Cognitive changes under memantine according to vitamin D status in Alzheimer patients: An exposed/unexposed cohort pilot study. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded Clinical Trial in Surgical Patients. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

A phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects. [2023]

14. Brazil pubmed.ncbi.nlm.nih.gov

Therapeutic role of memantine for the prevention of cognitive decline in cancer patients with brain metastasis receiving whole-brain radiotherapy: a narrative review. [2023]