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

NCT06919926 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB004378505R01AG061091
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hippocampal Overactivity; Dementia

Outcome Measures

Primary Outcomes (1)

• Change in hippocampal overactivity as measured by fMRI (functional Magnetic Resonance Imaging)

  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 Outcomes (1)

• Change in functional connectivity measures as measured by fMRI (functional Magnetic Resonance Imaging)

  Week 2, Week 8

Study Arms (2)

AGB101 first, then placebo

EXPERIMENTAL

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: AGB101; Drug: Placebo

placebo first, then AGB101

EXPERIMENTAL

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: AGB101; Drug: Placebo

Interventions

AGB101 DRUG

low-dose levetiracetam, 220 mg, extended release tablet

Also known as: levetiracetam

AGB101 first, then placebo; placebo first, then AGB101

Placebo DRUG

placebo capsule

Also known as: sugar pill

AGB101 first, then placebo; placebo first, then AGB101

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects between 50 and 80 years old (inclusive) in good general health:
• Willing and able to consent and participate for the duration of the study.
• Have eighth-grade education or good work history sufficient to exclude mental retardation.
• Have visual and auditory acuity adequate for neuropsychological testing.
• Have proficient fluency of the native local language to participate in all the neuropsychological test assessments.
• 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.
• Have normal cognition as defined by the following criteria:
• 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)
• No memory complaint reported by the subject or his/her study partner.
• Evidence of normal memory function documented by a normal score on the Buschke Selective Reminding Test Immediate and Delayed Recall or equivalent test.
• A Clinical Dementia Rating Scale (CDR) global score of 0 with a memory box score of 0.
• Antidepressants must be at a stable dose for 1 month prior to screening and expected to remain stable throughout the study.
• Willing and able to undergo repeated MRI scans (3 Tesla) with no contraindications to MRI.
• Willing to allow collection of blood for apolipoprotein E (ApoE) genotyping and banking.
• Willing and able to undergo a Tau positron emission tomography (PET) scan with 18F MK-6240 tracer.

You may not qualify if:

• Use of anticonvulsant or anticoagulant medications within 1 month prior to the baseline visit.
• 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.
• History of hypersensitivity or lack of tolerability to AGB101 (levetiracetam).
• Severe renal impairment (creatinine clearance of \< 30 mL/minute) or undergoing hemodialysis.
• Diagnosis of major depression within the last 3 years or prior diagnosis of schizophrenia, bipolar disorder or other psychotic disorder.
• 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.
• History of alcohol or substance abuse or dependence within the past 3 years (DSM-5 criteria).
• Any significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol requirements.
• 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.
• Current suicidal ideation.
• Female subjects must not be pregnant or lactating.
• Any other reason, which in the opinion of the investigator would confound proper interpretation of the study.

Sponsors & Collaborators

• Johns Hopkins University: lead
• AgeneBio: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

RECRUITING

Related Publications (5)

• Yassa MA, Lacy JW, Stark SM, Albert MS, Gallagher M, Stark CE. Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults. Hippocampus. 2011 Sep;21(9):968-79. doi: 10.1002/hipo.20808. Epub 2010 May 20.

  PMID: 20865732 BACKGROUND

• O'Brien JL, O'Keefe KM, LaViolette PS, DeLuca AN, Blacker D, Dickerson BC, Sperling RA. Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology. 2010 Jun 15;74(24):1969-76. doi: 10.1212/WNL.0b013e3181e3966e. Epub 2010 May 12.

  PMID: 20463288 BACKGROUND

• Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of 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):280-92. doi: 10.1016/j.jalz.2011.03.003. Epub 2011 Apr 21.

  PMID: 21514248 BACKGROUND

• Dickerson BC, Salat DH, Greve DN, Chua EF, Rand-Giovannetti E, Rentz DM, Bertram L, Mullin K, Tanzi RE, Blacker D, Albert MS, Sperling RA. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology. 2005 Aug 9;65(3):404-11. doi: 10.1212/01.wnl.0000171450.97464.49.

  PMID: 16087905 BACKGROUND

• Miller SL, Fenstermacher E, Bates J, Blacker D, Sperling RA, Dickerson BC. Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline. J Neurol Neurosurg Psychiatry. 2008 Jun;79(6):630-5. doi: 10.1136/jnnp.2007.124149. Epub 2007 Sep 10.

  PMID: 17846109 BACKGROUND

MeSH Terms

Conditions

Dementia

Interventions

Levetiracetam; Sugars

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Study Officials

• Arnold Bakker, Ph.D.

  Johns Hopkins University

  STUDY DIRECTOR

• Marilyn Albert, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caroline L Wagandt, BA

CONTACT

410-955-5057; cspeck1@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 9, 2025
• Study Start: April 17, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)