Clinical Trial Evaluating the Efficacy of AGB101 for Reducing Hippocampal Overactivity in Older Adults (AGB101-CN)

April 9, 2026 updated by: Johns Hopkins University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Caroline L Wagandt, BA
  • Phone Number: 410-955-5057
  • Email: cspeck1@jhmi.edu

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University School of Medicine
        • Contact:
        • Principal Investigator:
          • Marilyn Albert, Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Subjects must meet all of the following inclusion criteria at screening:

  1. Subjects between 50 and 80 years old (inclusive) in good general health:

    1. Willing and able to consent and participate for the duration of the study.
    2. Have eighth-grade education or good work history sufficient to exclude mental retardation.
    3. Have visual and auditory acuity adequate for neuropsychological testing.
    4. Have proficient fluency of the native local language to participate in all the neuropsychological test assessments.
  2. Have a study partner who has sufficient contact (≥ 2 hours per week) with the subject and can provide assessments of any changes and an independent evaluation of the subject's functioning.

  3. Have normal cognition as defined by the following criteria:

    1. Mini-Mental State Examination (MMSE) scores between 27 and 30 (inclusive; exceptions may be made for subjects with < 12 years of education at the discretion of the investigator)
    2. No memory complaint reported by the subject or his/her study partner.
    3. Evidence of normal memory function documented by a normal score on the Buschke Selective Reminding Test Immediate and Delayed Recall or equivalent test.
    4. A Clinical Dementia Rating Scale (CDR) global score of 0 with a memory box score of 0.
  4. Antidepressants must be at a stable dose for 1 month prior to screening and expected to remain stable throughout the study.
  5. Willing and able to undergo repeated MRI scans (3 Tesla) with no contraindications to MRI.
  6. Willing to allow collection of blood for apolipoprotein E (ApoE) genotyping and banking.
  7. Willing and able to undergo a Tau positron emission tomography (PET) scan with 18F MK-6240 tracer.
  8. If female participant or partner/spouse is of childbearing age, participant and/or partner must be willing to use an effective contraception for duration of the study and for 4 days after it. For women, effective contraception may be hormonal; for men, a condom.

Exclusion Criteria:

  • Subjects must not meet any of the following exclusion criteria at screening:

    1. Use of anticonvulsant or anticoagulant medications within 1 month prior to the baseline visit.
    2. Participation in a therapeutic clinical study for any medical or psychiatric indications within 1 month of the screening visit, or at any time during the study. Subjects must understand that participants may only enroll in this clinical study once; participants may not enroll in any other clinical study while participating in the current study, and participants may not participate in a clinical study of a drug, biologic, therapeutic device, or medical food, in which the last dose/administration was received within 1 month prior to screening.
    3. History of hypersensitivity or lack of tolerability to AGB101 (levetiracetam).
    4. Severe renal impairment (creatinine clearance of < 30 mL/minute) or undergoing hemodialysis.
    5. Any significant neurological disease such as Parkinson's disease, Alzheimer's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder (lifetime history; infant febrile seizures are not exclusionary), subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits, or known structural brain abnormalities, that in the opinion of the investigator might interfere with the conduct of the study.
    6. Diagnosis of major depression within the last 3 years or prior diagnosis of schizophrenia, bipolar disorder or other psychotic disorder.
    7. Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body that constitute a contraindication to having an MRI scan.
    8. History of alcohol or substance abuse or dependence within the past 3 years (DSM-5 criteria).
    9. Any significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol requirements.
    10. Any unstable medical condition that is likely to require new medical or surgical treatment during the course of the study and where such treatments might affect the collection of efficacy data.
    11. Current suicidal ideation.
    12. Female subjects must not be pregnant or lactating.
    13. Any other reason, which in the opinion of the investigator would confound proper interpretation of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AGB101 first, then placebo
AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 2 weeks, washout (4 weeks), then placebo capsule once daily for 2 weeks.
Drug: Placebo
placebo capsule
Other Names:
  • sugar pill
Drug: AGB101
low-dose levetiracetam, 220 mg, extended release tablet
Other Names:
  • levetiracetam
Experimental: placebo first, then AGB101
Placebo capsule once daily for 2 weeks, washout (4 weeks), then AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 2 weeks.
Drug: Placebo
placebo capsule
Other Names:
  • sugar pill
Drug: AGB101
low-dose levetiracetam, 220 mg, extended release tablet
Other Names:
  • levetiracetam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in hippocampal overactivity as measured by fMRI (functional Magnetic Resonance Imaging)
Time Frame: Week 2, Week 8
The primary efficacy evaluation is confirmation of target engagement demonstrated by reduction in hippocampal overactivity comparing the end of the active treatment period compared to the end of the placebo treatment condition as measured by task-based functional magnetic resonance imaging.
Week 2, Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in functional connectivity measures as measured by fMRI (functional Magnetic Resonance Imaging)
Time Frame: Week 2, Week 8
Functional connectivity measures comparing the end of the active treatment period to the end of the placebo treatment condition as measured by resting state fMRI (functional Magnetic Resonance Imaging).
Week 2, Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Institute on Aging (NIA)
AgeneBio

Investigators

  • Study Director: Arnold Bakker, Ph.D., Johns Hopkins University
  • Principal Investigator: Marilyn Albert, PhD, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2025

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

April 2, 2025

First Submitted That Met QC Criteria

April 2, 2025

First Posted (Actual)

April 9, 2025

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 9, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00437850
  • 5R01AG061091 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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