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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether memantine, a medication, and a special exercise program can address cognitive issues, such as memory and thinking problems, in women undergoing chemotherapy for breast cancer. Participants will be divided into three groups: one receiving memantine and guided exercise, another receiving memantine and pre-recorded exercise sessions, and a third group with only the exercise sessions. Women with stage I-III breast cancer, who are at least 50 years old and have mild cognitive concerns during chemotherapy, might be suitable candidates. The study aims to determine if these treatments improve cognitive function and are easy to adhere to. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that memantine is generally safe for patients. In earlier studies, memantine helped prevent memory and thinking problems during breast cancer chemotherapy. These studies found that memantine was well-tolerated, with most participants not experiencing serious side effects.

When combined with exercise, early research suggests memantine remains safe. This combination has been studied for its potential to improve memory and thinking skills. Current findings indicate that this combination is tolerable for participants, as it did not cause significant negative effects.

While the treatment appears safe, joining a clinical trial may involve unknown risks. It is advisable to consult a doctor about any concerns before participating in a study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine memantine, a drug typically used for Alzheimer's, with targeted exercise to tackle cognitive impairment in breast cancer patients. Unlike standard options that may focus on medication alone, this approach leverages the neuroprotective properties of memantine alongside the physical and cognitive benefits of exercise. Memantine is thought to help by blocking certain receptors in the brain that, when overactivated, can contribute to cognitive decline. The combination with exercise, specifically the Get Real & Heel program, aims to enhance brain health in a holistic way, offering a potentially more comprehensive solution than existing treatments.

What evidence suggests that this trial's treatments could be effective for cognitive impairment in breast cancer?

Studies have shown that memantine can help maintain or improve thinking skills in people with cancer-related cognitive problems. In some trials, up to 91% of participants experienced stable or improved thinking abilities. Research has also shown that exercise can enhance brain function and memory. This trial will explore different combinations of these interventions: one group will receive memantine and guided exercise sessions, another will receive memantine and access to pre-recorded exercise sessions, and a third group will have access to pre-recorded exercise sessions without memantine. Combining memantine with exercise might further increase these benefits, and this approach is being studied for its potential to support brain health in breast cancer patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Zev Nakamura, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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

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

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

I am 50 years old or older.

Exclusion Criteria

Allergy to memantine

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

Exceeding 30 min vigorous or 60 min moderate physical activity per week

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

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A phase II single‐arm trial of memantine for prevention of ... This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06727773

Memantine and Exercise to Improve Cognitive Function ... Compared to other cancers and treatments, cognitive decline has been most robustly described in breast cancer and following chemotherapy with up to 75% self- ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.12109

A single-arm feasibility trial of memantine to prevent ... Among evaluable participants, 92% reported taking ≥ 90% of scheduled doses. Only 36% self-reported cognitive decline, while no change was ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36645168/

A phase II single-arm trial of memantine for ... - PubMed Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across ...

5. trialx.com trialx.com/clinical-trials/listings/297939/memantine-and-exercise-to-improve-cognitive-function-and-modulate-biological-pathways-of-cognitive-decline-during-chemotherapy-in-breast-cancer/

Memantine and Exercise to Improve Cognitive Function ... The primary objective of this study is to demonstrate the feasibility and acceptability of MEM+EX during breast cancer chemotherapy. Secondarily ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04033419

Memantine for Prevention of Cognitive Decline in Patients ... This is a one-arm phase II interventional study in patients with breast cancer to investigate whether memantine can prevent cognitive decline during ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT365972

A single-arm feasibility trial of memantine to prevent ... Our findings suggest that memantine is a safe and feasible intervention for chemotherapy-related cognitive decline and may ameliorate cognitive loss.