Memantine for Alzheimer's Disease

Overseen By Joyce Sprock

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Diego

Must not be taking: Opioids, Amantadine, Riluzole, others

Disqualifiers: Heart disease, Cancer, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the medication memantine affects brain functions and symptoms in people with Alzheimer's Disease. Participants will receive either memantine or a placebo (a pill with no active medication) to compare results. The goal is to determine if memantine can improve memory and daily function in people with Alzheimer's. It suits those with a confirmed Alzheimer's diagnosis, who are medically stable, and have a caregiver. As a Phase 4 trial, memantine is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including amantadine, riluzole, other pro-cognitive medications, and opioids, before participating.

What is the safety track record for memantine?

Research has shown that memantine is generally safe for treating Alzheimer's disease. Studies have found that patients can use memantine both short-term and long-term without major problems. The side effects resemble those seen with a placebo, a harmless pill used for comparison in studies.

Memantine has undergone many trials and is rated highly for patient tolerance, meaning most people can take the treatment without serious issues.

Overall, the FDA has approved memantine for treating Alzheimer's disease, indicating it has been thoroughly tested to ensure safety and effectiveness. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Memantine is unique because it offers a different approach to treating Alzheimer's disease compared to standard options like cholinesterase inhibitors (donepezil, rivastigmine, galantamine), which increase the levels of neurotransmitters in the brain. Unlike these treatments, memantine works by blocking NMDA receptors to prevent excessive calcium influx into brain cells, which can be toxic and lead to cell death. This mechanism may help protect nerve cells from damage, potentially slowing down the progression of symptoms. Researchers are excited about memantine because it could provide additional benefits when combined with existing therapies, offering a more comprehensive approach to managing Alzheimer's disease.

What is the effectiveness track record for memantine in treating Alzheimer's Disease?

Research has shown that memantine, which participants in this trial may receive, benefits people with moderate to severe Alzheimer's disease. Studies have found that memantine can slow the decline of brain function, helping patients maintain their abilities longer. It has improved thinking and memory skills. Some research even suggests that memantine might reduce the risk of death from any cause in people with dementia. As an approved treatment for Alzheimer's, memantine is a dependable choice for managing symptoms. ^{1 3 6 7 8}

Who Is on the Research Team?

Neal Swerdlow, M.D., Ph.D.

Principal Investigator

UCSD

Are You a Good Fit for This Trial?

This trial is for people aged 50-83 with Alzheimer's, confirmed by specific tests and having certain cognitive scores. Participants must have a caregiver, be able to walk, hear well at a specific frequency, and be medically stable without serious illnesses or psychiatric conditions other than Alzheimer's.

Inclusion Criteria

I have been diagnosed with Alzheimer's disease by a research center.

Your memory and thinking test scores are between 10-22 for MMSE or 15-24 for MOCA.

I am between 50 and 83 years old.

Exclusion Criteria

You are currently participating in cognitive therapy.

You have used illegal drugs that were not prescribed by a doctor.

I am currently taking medications like amantadine, riluzole, or opioids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive memantine or placebo to test effects on brain functions and symptoms of Alzheimer's Disease

24 weeks

Visits at 0, 8, 16, and 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Memantine
• Placebo

Trial Overview The study is examining how memantine affects brain function and symptoms in Alzheimer's patients compared to a placebo (a substance with no active drug). Patients will not know if they're getting the real medication or the placebo.

How Is the Trial Designed?

Group I: Memantine Active Control 1 Intervention

EAIP are assessed 210 (PPI) and 345 min (MMN, ASSR) after administration of placebo or memantine (MEM 20 mg po), in a randomized order double-blind design. In this arm subjects are administered MEM 20 mg. Pills look identical so both the subject and research staff are blind to condition.

Group II: Placebo Placebo Group 1 Intervention

EAIP are assessed 210 (PPI) and 345 min (MMN, ASSR) after administration of placebo or MEM (20 mg po), in a randomized order double-blind design. In this arm subjects are administered placebo. Pills look identical to MEM so both the subject and research staff are blind to condition.

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

Approved in European Union as Ebixa for:

• Alzheimer's disease

Approved in United States as Namenda for:

• Moderate to severe Alzheimer's disease

Approved in United States as Namenda XR for:

• Moderate to severe Alzheimer's disease

Approved in United States as Namzaric for:

• Moderate to severe Alzheimer's disease

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

Memantine is a well-established treatment for Alzheimer's disease, acting as a noncompetitive antagonist of NMDA receptors, which helps relieve symptoms but does not cure the disease.

Since its introduction in 1989, memantine has become the second most commonly used dementia drug worldwide, highlighting its significance in managing Alzheimer's symptoms despite its limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basic information about memantine and its treatment of Alzheimer's disease and other clinical applications. Tang, BC., Wang, YT., Ren, J.[2023]

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 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]

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 an FDA-approved treatment for moderate to severe Alzheimer's disease, demonstrating both safety and efficacy as a standalone therapy or in combination with cholinesterase inhibitors.

Research suggests that memantine may also have potential therapeutic effects in other neuropsychiatric conditions, warranting further investigation into its broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine: a review of studies into its safety and efficacy in treating Alzheimer's disease and other dementias. Thomas, SJ., Grossberg, GT.[2022]

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 effective treatment for moderate-to-severe Alzheimer's disease, acting as a neuroprotective agent by blocking excessive calcium influx through NMDA receptors, which helps maintain normal brain signaling.

While memantine does not cure or reverse Alzheimer's disease, it can enhance cognitive function and is safe to use in combination with other treatments, as supported by various clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Glutamate-related excitotoxicity neuroprotection with memantine, an uncompetitive antagonist of NMDA-glutamate receptor, in Alzheimer's disease and vascular dementia]. Tanović, A., Alfaro, V.[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 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, 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]

Citations

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

Memantine: efficacy and safety in mild-to-severe Alzheimer's ... The results of this study showed that when treatment response required cognitive improvement relative to baseline, memantine yielded higher response rates than ...

2. 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.

3. 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 ... CONCLUSION. Our results suggest that the use of memantine in patients with dementia may be associated with a reduction in all-cause mortality.

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

Memantine in Moderate-to-Severe Alzheimer's Disease Thus, our data indicate that memantine reduces decline in patients with moderate-to-severe Alzheimer's disease.

5. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-018-0457-9

a network meta-analysis of 41 randomized controlled trials Memantine 20 mg showed the highest probability (SUCRA 83.5%) of receiving the highest treatment acceptability rating, followed by donepezil 10 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18558791/

Memantine for the treatment of Alzheimer's disease Both short- and long-term memantine treatment of patients with AD is safe and well tolerated, with an adverse event profile similar to that of placebo.

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

Memantine - accessdata.fda.gov The efficacy and safety data presented in the clinical trial sections were obtained from these patients. There were no clinically meaningful differences in most ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0168365924000622

Alzheimer's disease current therapies, novel drug delivery ... This review paper aims to offer an insightful overview of disease pathogenesis, current FDA-approved drugs, and drugs in different clinical phases.