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Hippocampal OveractivityPhase 2AGB101-CNNCT06919926

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

A Phase 2 study testing AGB101 in people with Hippocampal Overactivity and Dementia, run by Johns Hopkins University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Hippocampal Overactivity, Dementia
What is being tested?
AGB101
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteUnited States
Study dates
17 Apr 2025to May 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • Subjects must not meet any of the following exclusion criteria at screening:
  • 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.
  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21287

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
AGB101, Placebo
Medical subject headings
Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AGB101Drug

    Also called levetiracetam

    low-dose levetiracetam, 220 mg, extended release tablet

  • PlaceboDrug

    Also called sugar pill

    placebo capsule

Study groups in NCT06919926
Study groupRoleWhat they receive
AGB101 first, then placeboExperimentalAGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 2 weeks, washout (4 weeks), then placebo capsule once daily for 2 weeks.
Receives: Drug: AGB101; Drug: Placebo
placebo first, then AGB101ExperimentalPlacebo capsule once daily for 2 weeks, washout (4 weeks), then AGB101 (low-dose levetiracetam, 220 mg, extended release tablet) once daily for 2 weeks.
Receives: Drug: AGB101; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 2, Week 8

Secondary outcomes (1)

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

    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).

    Measured: Week 2, Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2025
  2. Study start17 Apr 2025
  3. Primary completionMay 2027 (estimated)
  4. Study completionMay 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06919926
Sponsor's protocol ID
IRB00437850
Other IDs
5R01AG061091
Acronym
AGB101-CN
Status last verified
Aug 2026
First submitted
2 Apr 2025
Last updated
31 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 20865732

  • 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.

    PubMed 20463288

  • 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.

    PubMed 21514248

  • 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.

    PubMed 16087905

  • 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.

    PubMed 17846109

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AGB101 in people with Hippocampal Overactivity and Dementia, run by Johns Hopkins University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in hippocampal overactivity as measured by fMRI (functional Magnetic Resonance Imaging) (time frame: Week 2, Week 8). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06919926, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.

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