Memantine for Preventing Alzheimer's Disease

Overseen By Amy Fansler

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Virginia

Must be taking: Memantine

Must not be taking: AChE inhibitors, Acetazolamide, Methazolamide, Amantadine

Disqualifiers: Severe renal impairment, Neurodegenerative disorder, Active cancer, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 97 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether memantine tablets can prevent Alzheimer's Disease before symptoms appear. Alzheimer's is a brain condition that can affect individuals many years before any issues become noticeable. Researchers aim to determine if this medication can stop or slow the brain changes leading to the disease. Suitable candidates for this trial are individuals aged 50 to 65 with a family history of dementia and a specific genetic marker (ApoE ε4) linked to Alzheimer's. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you do not take medications that raise the pH of your urine or certain drugs like acetazolamide, methazolamide, amantadine, ketamine, and dextromethorphan. If you are on these medications, you may need to stop them to participate.

Is there any evidence suggesting that memantine hydrochloride is likely to be safe for humans?

Research has shown that memantine is generally safe for people. The FDA has already approved it to treat moderate to severe Alzheimer's disease. Studies have found that most people tolerate it well, with side effects usually mild. Common side effects include headache, constipation, confusion, and dizziness.

While memantine is not a cure for Alzheimer's, it has effectively helped manage symptoms in those with the disease. This suggests that memantine could be a promising option for preventing Alzheimer's, but more research is needed to confirm its safety and effectiveness for this new use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care options for Alzheimer's, which typically focus on managing symptoms, Memantine Hydrochloride is being explored for its potential to actually prevent the disease. Memantine works by targeting NMDA receptors in the brain, helping to regulate glutamate activity, which is thought to contribute to Alzheimer’s progression. Researchers are excited about this treatment because it offers a different approach by potentially slowing down the disease process rather than just addressing symptoms.

What evidence suggests that memantine might be an effective treatment for Alzheimer's?

Research shows that memantine, which participants in this trial may receive, is approved for treating moderate to severe Alzheimer's disease. It helps slow the worsening of symptoms in these stages. In various Alzheimer's studies, memantine has demonstrated both healing and protective effects. While its use for prevention remains under investigation, the medication has been proven to lower the overall death rate in dementia patients. This suggests it might help delay or prevent Alzheimer's disease before symptoms start. ^{4 6 7 8 9}

Who Is on the Research Team?

Anelyssa D'Abreu, MD

Principal Investigator

Associate Professor of Neurology

Carol Manning, PhD

Principal Investigator

Professor of Neurology

Are You a Good Fit for This Trial?

This trial is for people aged 50-65 with a family history of dementia and the ApoE ε4 allele, which increases Alzheimer's risk. Participants must be generally healthy or stable on medication, have good vision and hearing for tests, a MOCA score of 27+, and adequate kidney function. They can't join if they have MRI/PET scan issues, recent major surgery, are in another drug study, need certain medications that affect cognition or urine pH, or have significant health problems.

Inclusion Criteria

My kidneys work well enough (CrCl ≥ 30 mL/min).

I carry one or two copies of the ApoE ε4 gene.

My cognitive function is good, with a MOCA score of 27 or above.

Exclusion Criteria

Current participation in an interventional study with an investigational drug component

I have a brain disorder that affects my memory or thinking.

I haven't had major surgery in the last 8 weeks and don't plan any during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive memantine hydrochloride or placebo with titration up/down

97 weeks

Regular visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Memantine Hydrochloride Tablets
• Placebo

Trial Overview The study is testing whether taking Memantine Hydrochloride Tablets can prevent Alzheimer's Disease in individuals at risk due to genetic factors. It compares the effects of memantine against a placebo (a pill without active medicine) to see if it helps maintain cognitive functions.

How Is the Trial Designed?

Group I: Memantine hydrochloride Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Memantine Hydrochloride Tablets is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Ebixa for:

• Moderate to severe Alzheimer's disease

Approved in United States as Namenda for:

• Moderate to severe Alzheimer's disease

Approved in Japan as Various brand names for:

• Alzheimer's disease

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

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]

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]

In patients with moderate to severe Alzheimer's disease, memantine showed a statistically significant but clinically small positive effect on cognition and daily functioning in three out of four randomized controlled trials, indicating it may help improve some symptoms in this population.

For patients with mild to moderate Alzheimer's disease, the addition of memantine to donepezil demonstrated positive effects on cognition and daily living activities, suggesting it could be beneficial when used in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the use of memantine in Alzheimer's disease. van Marum, RJ.[2021]

In a 5-year study analyzing cognitive decline in Huntington's disease patients, memantine use did not show any significant clinical benefits compared to non-users.

The study utilized linear mixed effect models to compare memantine users and non-users, indicating that memantine may not be effective in altering the course of cognitive decline in Huntington's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine Use and Cognitive Decline in Huntington's Disease: An Enroll-HD Study. Ogilvie, AC., Schultz, JL.[2023]

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]

In a 28-week clinical trial involving 252 patients with moderately-severe to severe Alzheimer's disease, memantine significantly increased the likelihood of patients remaining autonomous, with a threefold increase in odds compared to those on placebo.

Memantine not only helps maintain daily living capabilities but also delays the transition from autonomy to dependence in Alzheimer's patients, highlighting its potential to improve quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine enhances autonomy in moderate to severe Alzheimer's disease. Rive, B., Vercelletto, M., Damier, FD., et al.[2013]

Memantine is an NMDA receptor antagonist that provides neuroprotective effects by reducing glutamate overstimulation, making it effective for treating moderate to severe Alzheimer's dementia without the adverse effects commonly seen with stronger antagonists.

It is the first drug approved for Alzheimer's treatment in both Europe and the United States, and ongoing research is exploring its potential benefits in earlier stages of Alzheimer's and other types of dementia, particularly when used in combination with cholinesterase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinical relevance of memantine use]. Sobów, T.[2013]

In a 4-month observational study involving 377 outpatients with moderate to severe Alzheimer's disease, memantine was found to be well-tolerated and effective in improving cognitive function, daily living activities, and overall global function.

The benefits of memantine were observed in both patients who had previously received treatment and those who were new to the medication, indicating its broad applicability in real-life settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine in moderate to severe Alzheimer's disease: an observational post-marketing study. Rainer, M., Wuschitz, A., Jagsch, C., et al.[2021]

Memantine, used for treating moderate to severe Alzheimer's disease, has been shown to have a favorable safety and tolerability profile, with adverse events similar in frequency to those experienced by patients on placebo, based on data from 2311 patients in six trials lasting at least 24 weeks.

The analysis indicates that both short- and long-term treatment with memantine is safe, with minimal adverse effects, and discontinuation rates due to side effects were comparable between memantine and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine for the treatment of Alzheimer's disease: tolerability and safety data from clinical trials. Farlow, MR., Graham, SM., Alva, G.[2021]

In a study of 201 outpatients with moderate-to-severe Alzheimer's disease, memantine demonstrated a short-term efficacy in improving cognitive and behavioral symptoms, with effects persisting over a two-year follow-up period.

While 8% of patients discontinued memantine due to side effects, about 20% of patients in both treatment groups showed no deterioration in their condition at six months and one year, indicating a degree of sustained benefit from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine in Alzheimer's disease: experience in an Alzheimer's disease assessment unit. Sinforiani, E., Pasotti, C., Chiapella, L., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16906789/

Memantine: a review of its use in Alzheimer's disease Memantine is an effective pharmacotherapeutic agent, and currently the only approved option, for the treatment of moderate to severe Alzheimer's disease.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0028390823003271

Memantine: Updating a rare success story in pro-cognitive ... Considered one of the rare exceptions, memantine has consistently demonstrated restorative and prophylactic properties in many AD models.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05063851

The Use of Memantine for Prevention of Alzheimer's Disease The minimum recommended interval between dose increases is one week. The dosage shown to be effective in controlled clinical trials is 20 mg/day. Participant ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.70071

Effect of long‐term treatment with memantine on mortality in ... Our results suggest that the use of memantine in patients with dementia may be associated with a reduction in all-cause mortality.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa013128

Memantine in Moderate-to-Severe Alzheimer's Disease Memantine-treated patients showed significantly less deterioration in their functional Alzheimer's disease stage, as measured by the Functional Assessment ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2654628/

Memantine: efficacy and safety in mild-to-severe Alzheimer's ... In this article, we review the evidence for the use of memantine in patients with AD, ranging from the mild to severe stages of disease.

7. mayoclinic.org mayoclinic.org/drugs-supplements/memantine-oral-route/description/drg-20067012

Memantine (oral route) - Side effects & dosage Memantine is used to treat moderate to severe Alzheimer's disease. Memantine is not a cure for Alzheimer's disease but it can help people with the disease.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/021487s025lbl.pdf

Memantine - accessdata.fda.gov The efficacy and safety data presented in the ... The effectiveness of NAMENDA as a treatment for patients with moderate to severe Alzheimer's disease.

9. alz.org alz.org/alzheimers-dementia/treatments/medications-for-memory

Medications for Memory, Cognition & Dementia-Related ... Memantine (Namenda®): approved for moderate-to-severe Alzheimer's disease. Can cause side effects, including headache, constipation, confusion and dizziness.