Memantine for Preventing Alzheimer's Disease

Recruiting in Palo Alto (17 mi)

Overseen by Anelyssa D'Abreu, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing memantine hydrochloride to see if it can prevent Alzheimer's Disease in people aged 50-65 who are at higher risk due to genetics and family history. The medication aims to protect brain cells from damage. Memantine hydrochloride is an FDA-approved drug used to treat Alzheimer's disease by reducing neurodegeneration in the hippocampus and cerebral cortex.

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.

What evidence supports the effectiveness of the drug Memantine for preventing Alzheimer's Disease?

Memantine is known to help improve symptoms and slow down the progression of moderate to severe Alzheimer's Disease by blocking excessive activity of NMDA receptors, which are involved in brain cell communication. It has shown benefits in cognition, daily activities, and overall function in patients with Alzheimer's Disease. ^{1 2 3 4 5}

Is memantine safe for humans?

Memantine has been shown to have a good safety and tolerability profile in clinical trials for Alzheimer's disease, with adverse events occurring at rates similar to placebo. It is generally well-tolerated and does not interfere with cognitive functions. ^{1 4 6 7 8}

How is the drug Memantine unique in preventing Alzheimer's disease?

Memantine is unique because it is an NMDA receptor antagonist that helps protect brain cells by reducing overstimulation from glutamate, which can be harmful. Unlike other treatments, it is specifically used for moderate to severe stages of Alzheimer's and has shown potential benefits in other types of dementia as well. ^{1 5 8 9 10}

Research Team

Carol Manning, PhD

Principal Investigator

Professor of Neurology

Anelyssa D'Abreu, MD

Principal Investigator

Associate Professor of Neurology

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Memantine Hydrochloride Tablets (NMDA receptor antagonist)
• Placebo (Drug)

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.

Participant Groups

Group I: Memantine hydrochloride Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Memantine Hydrochloride Tablets is already approved in Japan for the following indications:

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+

James E. Ryan

University of Virginia

Chief Executive Officer since 2018

J.D. from Harvard Law School

Nikki Hastings

University of Virginia

Chief Medical Officer since 2018

Ph.D. in Biomedical Engineering from University of Virginia

Findings from Research

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 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]

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 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 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]

References

1. India pubmed.ncbi.nlm.nih.gov

Memantine: pharmacological properties and clinical uses. [2013]

2. Austria pubmed.ncbi.nlm.nih.gov

Memantine in moderate to severe Alzheimer's disease: an observational post-marketing study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Memantine enhances autonomy in moderate to severe Alzheimer's disease. [2013]

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

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

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

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

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

Memantine for the treatment of Alzheimer's disease: tolerability and safety data from clinical trials. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Memantine in Alzheimer's disease: experience in an Alzheimer's disease assessment unit. [2022]

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

Memantine hydrochloride: pharmacological and clinical profile. [2017]

9. Poland pubmed.ncbi.nlm.nih.gov

[The clinical relevance of memantine use]. [2013]

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

Update on the use of memantine in Alzheimer's disease. [2021]