Epileptic Hippocampus in Alzheimer's Disease

NCT05899764 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-001000
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The major goals of the study are to 1) characterize hippocampal activity in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and AD who have suspected hippocampal epileptic activity based on scalp EEG recordings from IRB # 21-001603; 2) study the efficacy of brivaracetam to suppress epileptic activity and pathological high frequency oscilations (pHFOs) during hippocampal depth electrode and scalp EEG in patients with MCI and AD; and 3) investigate the effects of brivaracetam on cognition in an open-label pilot study.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Keywords

Alzheimer's Disease; Mild Cognitive Impairment; Epileptic Activity; Pathological High Frequency Oscillations; Depth Electrode; Brivaracetam

Outcome Measures

Primary Outcomes (2)

• Brivaracetam on Cognition

  To determine the efficacy of brivaracetam to improve cognitive function for the following task at 3 months while taking brivaracetam oral tablets: Stroop interference naming (number correct)

  3 months

• Brivaracetam on Cognition

  To determine the efficacy of brivaracetam to improve cognitive function for the following task at 3 months while taking brivaracetam oral tablets: Virtual Route Learning Test (VRLT)

  3 months

Secondary Outcomes (9)

• Brivaracetam on Cognition

  12 months

• Brivaracetam on Cognition

  12 months

• Brivaracetam on Cognition

  12 months

• Brivaracetam on Functional Decline

  12 months

• Brivaracetam and Plasma Biomarkers

  12 months

Study Arms (1)

BRIV Experimental

EXPERIMENTAL

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.

Drug: Brivaracetam

Interventions

Brivaracetam DRUG

* Intravenous administration: 25 mg or 50 mg will be administered depending on its effects on epileptic activity during a hospital stay where simultaneous EEG and depth electrode recordings will be measuring epileptic activity. * Oral administration: Subjects will take 25mg or 50mg twice a day for 12 months. The dosage will depend on its effects on epileptic activity. Brivaracetam levels will be measured on months 3, 6 and 12.

Also known as: Briviact, Brivajoy

BRIV Experimental

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet research criteria for mild cognitive impairment (Albert et al. 2011) or Alzheimer's disease (McKhann et al. 2011) with high biomarker probability of Alzheimer's disease pathophysiology
• Ages 45 to 70
• Epileptic activity and/or pHFOs in temporal or fronto-temporal electrodes
• 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.

You may not qualify if:

• Risk factors for epileptic activity besides neurodegenerative disease
• Concurrent use of antiseizure medications
• Severe periventricular white matter disease
• Clinically significant lacunar infarcts
• Anticoagulant use
• Significant systemic medical illness:
• History of Korsakoff's syndrome
• Alcohol or substance abuse preceding dementia \& still present within 5 years of onset
• Untreated vitamin B12 or folate deficiency
• History of head trauma with persistent deficits
• Untreated syphilis
• History of multiple sclerosis or another neuro-inflammatory disorder
• History of vascular or multi-infarct dementia
• Diagnosis of Huntington's disease
• History of normal pressure hydrocephalus

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

Mary S. Easton Center for Alzheimer's Research and Care

Los Angeles, California, 90095-1769, United States

Location

Related Publications (7)

• Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.

  PMID: 21514249 BACKGROUND

• McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.

  PMID: 21514250 BACKGROUND

• Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984 Nov;141(11):1356-64. doi: 10.1176/ajp.141.11.1356.

  PMID: 6496779 BACKGROUND

• Stephen LJ, Brodie MJ. Brivaracetam: a novel antiepileptic drug for focal-onset seizures. Ther Adv Neurol Disord. 2017 Nov 23;11:1756285617742081. doi: 10.1177/1756285617742081. eCollection 2018.

  PMID: 29399049 BACKGROUND

• Vossel KA, Beagle AJ, Rabinovici GD, Shu H, Lee SE, Naasan G, Hegde M, Cornes SB, Henry ML, Nelson AB, Seeley WW, Geschwind MD, Gorno-Tempini ML, Shih T, Kirsch HE, Garcia PA, Miller BL, Mucke L. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurol. 2013 Sep 1;70(9):1158-66. doi: 10.1001/jamaneurol.2013.136.

  PMID: 23835471 BACKGROUND

• Vossel KA, Ranasinghe KG, Beagle AJ, Mizuiri D, Honma SM, Dowling AF, Darwish SM, Van Berlo V, Barnes DE, Mantle M, Karydas AM, Coppola G, Roberson ED, Miller BL, Garcia PA, Kirsch HE, Mucke L, Nagarajan SS. Incidence and impact of subclinical epileptiform activity in Alzheimer's disease. Ann Neurol. 2016 Dec;80(6):858-870. doi: 10.1002/ana.24794. Epub 2016 Nov 7.

  PMID: 27696483 BACKGROUND

• Vossel K, Ranasinghe KG, Beagle AJ, La A, Ah Pook K, Castro M, Mizuiri D, Honma SM, Venkateswaran N, Koestler M, Zhang W, Mucke L, Howell MJ, Possin KL, Kramer JH, Boxer AL, Miller BL, Nagarajan SS, Kirsch HE. Effect of Levetiracetam on Cognition in Patients With Alzheimer Disease With and Without Epileptiform Activity: A Randomized Clinical Trial. JAMA Neurol. 2021 Nov 1;78(11):1345-1354. doi: 10.1001/jamaneurol.2021.3310.

  PMID: 34570177 RESULT

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Keith A Vossel, MD, MSc

  Mary S. Easton Center at UCLA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katy A Figueroa, Bachelor of Science

CONTACT

310-206-8993; kafigueroa@mednet.ucla.edu

Sydney R Kilgore, BA

CONTACT

310-825-3198; skilgore@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Center Director at the Mary S. Easton Center for Alzheimer's Disease Research and Professor of Neurology

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: June 12, 2023
• Study Start: January 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: January 27, 2026

Record last verified: 2025-06

Locations

US (1)