NCT06919926

Clinical Trial Evaluating the Efficacy of AGB101 for Reducing Hippocampal Overactivity in Older Adults

A Randomized, Within-subject, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of AGB101 (Low-dose Levetiracetam, 220 mg, Extended Release Tablet) for the Treatment of Hippocampal Overactivity in the Elderly

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: All
• Age: 50 Years – 80 Years
• Healthy volunteers: Accepted

Summary

This randomized, crossover, placebo controlled clinical study will assess the efficacy and safety of a slow release form of levetiracetam (AGB101) in the treatment of cognitively normal adults by measuring change in several imaging measures over the course of a two week treatment period.

Detailed description

In clinical studies, the magnitude of hippocampal over-activity longitudinally predicts subsequent cognitive decline/conversion to dementia, and hippocampal over-activity in subjects with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) is significantly correlated with the extent of neuronal injury affecting AD-specific regions of the brain. A previous study reported a significant correlation between greater hippocampal activation (fMRI) and more pronounced medial temporal lobe (MTL) atrophy (cortical thinning) indicative of AD-related neurodegeneration in subjects with MCI due to AD with a Clinical Dementia Rating (CDR) score of 0.5 selected by Alzheimer's Disease Neuroimaging Initiative (ADNI)-1 criteria. This supports a therapeutic rationale to reduce over-activity in order to slow or prevent neuronal injury. Modest hippocampal over-activity has also been observed in preclinical (asymptomatic) conditions in older adults. In previous studies, older adults showed increased hippocampal activation compared to young adults in the context of cognitive performance within the normal range for the participant's age. These findings suggest that hippocampal over-activity may be an opportunity for early intervention examining whether treatment of hippocampal over-activity early in the progression confers benefit to older adults at risk for AD dementia. The current study aims to test this hypothesis in cognitively normal subjects between the ages of 50 and 80.

Conditions

• Hippocampal Overactivity
• Dementia

Interventions

Type	Name	Description
DRUG	AGB101	low-dose levetiracetam, 220 mg, extended release tablet
DRUG	Placebo	placebo capsule

Timeline

• Start date: 2025-04-17
• Primary completion: 2027-05-01
• Completion: 2028-05-01
• First posted: 2025-04-09
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study