Brivaracetam for Alzheimer's Disease

(EHAD Trial)

Not yet recruiting at 1 trial location

Overseen By Sydney R Kilgore, BA

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, Los Angeles

Must not be taking: Antiseizure, Anticoagulants, Benzodiazepines, Narcotics

Disqualifiers: Severe white matter disease, Lacunar infarcts, Alcohol abuse, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests brivaracetam to determine if it can help individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD) who exhibit unusual brain activity, such as epileptic activity. Researchers aim to discover whether brivaracetam can reduce this unusual brain activity and improve cognitive function. The trial is open to those diagnosed with MCI or AD who show signs of epileptic brain activity, as identified in specific brain scans. Participants will undergo careful monitoring with brain scans while taking the medication in a hospital setting, followed by continued use at home. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially if they affect the central nervous system (like benzodiazepines or narcotics) or are antiseizure medications. However, you can continue taking cholinesterase inhibitors and memantine if your dosage has been stable for at least 30 days before joining the study.

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

Earlier studies found that brivaracetam was generally well-tolerated, with most people experiencing mild to moderate side effects. Research shows that few people stopped taking it due to side effects, suggesting that brivaracetam is relatively safe for humans. However, everyone can react differently to a treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard Alzheimer's treatments, which mainly focus on reducing symptoms or slowing disease progression, brivaracetam targets brain activity directly. Researchers are excited about brivaracetam because it is typically used to control seizures and may reduce abnormal brain activity linked to Alzheimer's. This potential new mechanism of action could offer a novel way to address cognitive decline by reducing epileptic events and high-frequency oscillations, which are thought to play a role in Alzheimer's disease.

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

Research has shown that brivaracetam, the investigational treatment in this trial, may help treat Alzheimer's disease by reducing seizure-related brain activity. In studies with mice that have Alzheimer's, brivaracetam lowered unusual brain activity and improved memory. It works by affecting a protein in the brain to calm nerve activity. Some research suggests it might cause temporary memory problems, but results vary. Overall, early research suggests brivaracetam could help manage brain activity in people with Alzheimer's. ^{4 6 7 8 9}

Who Is on the Research Team?

Keith A Vossel, MD, MSc

Principal Investigator

Mary S. Easton Center at UCLA

Are You a Good Fit for This Trial?

This trial is for adults aged 45-70 with mild cognitive impairment or Alzheimer's, showing specific epileptic activity on EEG. Participants need a reliable informant and must meet certain criteria including scoring above 18 on the Mini-Mental State Exam. Those with other risk factors for epilepsy, using antiseizure meds, significant brain lesions or systemic illnesses, or affecting CNS medications can't join.

Inclusion Criteria

Willing and able informant who has at least weekly contact with subject

Mini-Mental State Examination score of 18 or greater and/or Clinical Dementia Rating less than 2. These two examinations will be obtained from their participation in UCLA IRB#21-001603 or will be collected if subjects are referred by a clinician.

I have been diagnosed with mild cognitive impairment or Alzheimer's with a high likelihood of Alzheimer's disease.

Exclusion Criteria

Clinically significant lacunar infarcts

Risk factors for epileptic activity besides neurodegenerative disease

I am currently taking blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-surgical Assessment

Participants undergo MRV, MRA, gadolinium-enhanced MRI, and cognitive testing prior to electrode implantation

2 weeks

Multiple visits (in-person)

Surgical and Initial Treatment

Hippocampal depth electrodes are implanted, and brivaracetam is administered intravenously to assess its effects on epileptic activity

1 week

7 days (in-patient)

Long-term Treatment

Participants take brivaracetam orally for 1 year with follow-up visits for cognitive testing and biomarker analysis

12 months

3 visits (in-person) at 3, 6, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brivaracetam

Trial Overview The study aims to understand hippocampal activity in Alzheimer's patients with suspected epilepsy and test if Brivaracetam can reduce this abnormal activity and improve cognition. It involves monitoring through depth electrode and scalp EEG in an open-label pilot setup where all participants receive the drug.

How Is the Trial Designed?

Group I: BRIV Experimental Experimental Treatment 1 Intervention

25 subjects with MCI or AD who meet inclusion criteria will receive the drug: brivaracetam. A scalp EEG will record their brain activity for 6 days at the hospital. On nights 4 and 5, we will intravenously administer brivaracetam. Doses will vary depending on their effects on epileptic activity. We will determine whether brivaracetam 25 mg IV suppresses the number of epileptic events and pHFOs by \>50%, which is analogous to our preclinical investigations with this drug in AD models. If the 50% suppression is reached, the same dosage will be repeated the following night to ensure reproducibility. If the 50% suppression is not reached, then the dosage of brivaracetam will be increased to 50 mg the following night. Once the depth electrode is surgically removed, subjects will go home with a supply of brivaracetam. They will take the drug for 12 months.

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

Approved in European Union as Briviact for:

• Partial-onset seizures with or without secondary generalisation

Approved in United States as Briviact for:

• Focal (partial) onset seizures in epilepsy patients 1 month of age and older

Approved in Canada as Brivlera for:

• Partial-onset seizures with or without secondary generalisation

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10454935/

Antiseizure Medications in Alzheimer's Disease from ... Brivaracetam (BRV; 8.5 mg/kg/day), an AMS closely related to LEV, and ethosuximide (30 mg/mL) reduced spike-wave discharges (SWDs) detected in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4419386/

Brivaracetam, but not ethosuximide, reverses memory ... Ethosuximide and brivaracetam reduce spike-wave discharges in transgenic Alzheimer's disease mice. Transgenic Alzheimer's disease (AD) mice ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0920121122001450

Anti-epileptogenic effects of synaptic vesicle protein 2A ... Brivaracetam treatment displayed marked anti-epileptogenic effects in both aged and young Tg2576 mice, including when treatment is ceased prior to initiating ...

4. link.springer.com link.springer.com/article/10.1007/s43440-023-00564-3

The impact of brivaracetam on cognitive processes and ... BRV may cause transient memory deficits as well as anxiety disturbances. However, the results are varied and depend on the type of memory, used dose, and ...

5. mdpi.com mdpi.com/2673-9879/5/3/45

The Effect of Co-Administration of Levetiracetam or ... Preclinical studies indicate that levetiracetam and brivaracetam have beneficial effects in mouse models of Alzheimer's disease [16,17,18]. Furthermore, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10830775/

The impact of brivaracetam on cognitive processes and ... In preclinical studies, the BRV has been evaluated for the treatment of migraine [9], neuropathic pain [10], and Alzheimer's disease [11].

7. briviacthcp.com briviacthcp.com/safety

Safety & Tolerability | BRIVIACT® (brivaracetam) CV Safety Data · Most adverse events (AEs) were reported to be mild or moderate · Across all 3 trials, low discontinuation rates due to adverse events were observed ...

8. reference.medscape.com reference.medscape.com/drug/briviact-brivaracetam-1000083

Briviact (brivaracetam) dosing, indications, interactions, ... Use Caution/Monitor. Brivaracetam plasma concentration decreased by 21%. brivaracetam increases levels of phenytoin by decreasing metabolism. Use Caution/ ...

9. go.drugbank.com go.drugbank.com/drugs/DB05541

Brivaracetam: Uses, Interactions, Mechanism of Action View sample adverse effects data in our new Data Library! See the data ... Alzheimer's Disease (AD) / Mild Cognitive Impairment (MCI) · 1, somestatus, stop ...