Evaluating 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

This study is testing a new medication called AGB101 to see if it can help reduce brain activity in older adults who are not experiencing cognitive decline.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 50 Years to 80 Years
• Sex: All
• Sponsor: Johns Hopkins University (Academic / other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT06919926 on ClinicalTrials.gov

What this trial studies

This clinical trial assesses the efficacy and safety of AGB101, a slow-release form of levetiracetam, in reducing hippocampal overactivity in cognitively normal older adults aged 50 to 80. The study employs a randomized, crossover, placebo-controlled design, measuring changes in brain imaging over a two-week treatment period. The rationale is based on previous findings linking hippocampal overactivity to cognitive decline and Alzheimer's disease, suggesting that early intervention may slow or prevent neuronal injury. Participants will undergo neuropsychological testing and imaging assessments to evaluate the treatment's impact.

Who should consider this trial

Good fit: Ideal candidates are cognitively normal adults aged 50 to 80 who are in good general health and have a study partner for assessments.

Not a fit: Patients with significant cognitive impairment or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could help prevent or slow cognitive decline in older adults at risk for Alzheimer's disease.

How similar studies have performed: Previous studies have indicated a correlation between hippocampal overactivity and cognitive decline, supporting the potential for this novel approach.

Eligibility criteria

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.

Where this trial is running

Baltimore, Maryland

• Johns Hopkins University School of Medicine — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Marilyn Albert, PhD — Johns Hopkins University
• Study coordinator: Caroline L Wagandt, BA

Conditions Hippocampal Overactivity; Dementia