Levetiracetam for Alzheimer's Disease

(LAPSE Trial)

Overseen By Timothy R Malone, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Walter Reed National Military Medical Center

Must not be taking: Anti-epileptics

Disqualifiers: Epilepsy, Head trauma, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 6

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of levetiracetam, a medication, to manage symptoms in people with Alzheimer's disease who experience seizure-like brain activity. Researchers aim to determine if reducing this activity can improve memory issues, agitation, depression, and other related symptoms. The trial is open to individuals diagnosed with Alzheimer’s and noticeable neuro-psychiatric symptoms, such as mood changes or lack of interest in daily activities, who have a reliable caregiver to assist them. Participants will be monitored for a year to observe changes in their symptoms and quality of life with the treatment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires that your current medications, including acetylcholinesterase inhibitors, be stable for at least 4 weeks before starting. So, you don't have to stop them, but they need to be stable.

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

Research has shown that levetiracetam is generally safe for people with Alzheimer's disease. Studies have found that this medication does not negatively affect mood in these patients. It is often used in doses common for older adults with epilepsy, which also appear safe for those with Alzheimer's. So far, reports of major side effects in these groups have not emerged. This suggests that levetiracetam might be a safe option for people with Alzheimer's who also experience seizure-like activity. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard treatments for Alzheimer's, which typically focus on managing symptoms with medications like donepezil or memantine, levetiracetam is being explored for its ability to target epileptiform activity in the brain. This is unique because levetiracetam works by stabilizing neural activity, which might help reduce the abnormal brain activity seen in some Alzheimer's patients. Researchers are excited about levetiracetam because it offers a novel approach by potentially addressing a specific neurological aspect of Alzheimer's, rather than just treating its symptoms.

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

Research shows that levetiracetam might help people with Alzheimer's disease who have seizures. Earlier studies found that levetiracetam reduces seizures and improves thinking skills like memory and decision-making. It also decreases unusual brain activity in Alzheimer's cases. Although primarily used to prevent seizures, people with Alzheimer's have tolerated it well, without mood changes or major side effects. In this trial, all patients with epileptiform activity on initial screening EEG will receive levetiracetam for one year. These findings suggest that levetiracetam could help manage both seizures and related symptoms in Alzheimer's patients. ^{1 4 5 6 7}

Who Is on the Research Team?

Timothy R Malone, MD

Principal Investigator

Walter Reed National Military Medical Center

Are You a Good Fit for This Trial?

This trial is for people with Alzheimer's who show signs of agitation or depression (neuro-psychiatric symptoms) and have had a recent brain scan without seizure indicators. They must score below 26 on the MMSE, indicating cognitive impairment, and be on stable medication doses. A reliable caregiver is required to help them throughout the study.

Inclusion Criteria

My current medications have been the same for at least 4 weeks.

You have been diagnosed with Alzheimer's disease according to specific criteria.

Reliable caregiver willing and available to assist with medication administration, outcome measures

Exclusion Criteria

You are not expected to live for more than 12 months.

I have had encephalitis or meningitis in the past.

I have been diagnosed with epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Assessment

Participants undergo EEG to identify epileptiform activity

1 week

1 visit (in-person)

Treatment

Participants with epileptiform activity receive levetiracetam for 1 year

52 weeks

4 visits (in-person) at week 7, week 15, week 27, and month 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Levetiracetam

Trial Overview The LAPSE trial tests if Levetiracetam can reduce neuro-psychiatric symptoms in Alzheimer's patients with seizure-like activity. Participants will take this drug for a year while their symptoms, cognition, quality of life, and disease severity are monitored.

How Is the Trial Designed?

Group I: Levetiracetam Experimental Treatment 1 Intervention

All patients with epileptiform activity on initial screening EEG will receive levetiracetam for 1 year

Who Is Running the Clinical Trial?

Walter Reed National Military Medical Center

Lead Sponsor

Trials

149

Recruited

33,800+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0011393X25000232

Cognitive Effect of Levetiracetam in Patients with ... A 250 mg daily dose of LEV significantly improved spatial memory and executive function, whereas a 500 mg daily dose of LEV significantly enhanced global ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8477304/

Effect of Levetiracetam on Cognition in Patients With ... Levetiracetam treatment has been found to be well tolerated and successful at suppressing seizures among patients with AD and seizure disorders, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03489044

An Investigation of Levetiracetam in Alzheimer's Disease The anti-epileptic drug Levetiracetam can reduce abnormal brainwave activity and reverse memory deficits in a mouse model of Alzheimer's disease. Levetiracetam ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/epi4.13070

Safety, tolerability, and efficacy outcomes of the ... These pilot data show that levetiracetam is well tolerated in patients with AD who have not have seizures and has no detrimental effect on mood ...

5. pnas.org pnas.org/doi/10.1073/pnas.1121081109

Levetiracetam suppresses neuronal network dysfunction ... Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model | PNAS.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39400461/

a pilot, double-blind placebo-controlled crossover trial This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease who do not have a history of seizures.

7. medrxiv.org medrxiv.org/content/10.1101/2024.05.14.24307228v1

Safety, tolerability and efficacy outcomes of the ... Significance This pilot study demonstrates that levetiracetam was well tolerated in individuals with Alzheimer's disease, who do not have a ...