Network-Level Mechanisms for Preclinical Alzheimer's Disease Development

Medical College of Wisconsin

Status and phase: Completed; Phase 2

Conditions: APOE 4

Treatments: Drug: AGB101 220 mg; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03461861

R21AG056882-01 (U.S. NIH Grant/Contract)

PRO00031146

Details and patient eligibility

About

The purpose of this project is to test the hypothesis that AGB101 low dose levetiracetam extended release formulation can reduce abnormal hyperfunctional activity in the hippocampus in normal, healthy adults. The investigators will compare the functional connectivity results after taking AGB101 or placebo.

Full description

In this study the investigators want to find out whether the use of a perturbation, such as AGB101 low dose of levetiracetam extended release formulation, in healthy adults can reduce abnormal hippocampal network activity. The investigators also want to study whether this low dose of LEV can improve memory function.

Generic levetiracetam is a type of drug called an anti-epileptic or anti-seizure medication. It is FDA approved worldwide for adults and children as young as one month with seizures. It is a generic drug used in long-term epilepsy treatment. It is relatively safe and has an acceptable side-effect profile.

AGB101 has been developed as a novel extended release formulation of low dose levetiracetam (below clinically marketed doses for epilepsy) for slowing the progression of amnestic mild cognitive impairment.

It is known that age and the APOE 4 gene are important risk factors for late-onset Alzheimer's disease. Further studies have shown that cognitively normal, older adults have more hyperfunctional brain network activity, increased alpha beta accumulation, decreased memory function, and decreased brain volume, which is consistent with Alzheimer's disease patterns.

Enrollment: 26 patients

Sex: All

Ages: 55 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Fluent in English
• At least eight (8) years of education
• Geriatric Depression Scale (GDS) (62) score < 6
• Hachinski Ischemic Score ≤ 4
• Normal general cognitive function as well as 1) normal memory function, documented by MOCA score of 23 or greater, and a RBANS Delayed Memory Index score of 85 or greater.

Exclusion criteria

• Neurological disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or a history of significant head trauma or known structural brain abnormalities
• Major psychiatric disease or chronic unstable medical conditions
• History of drug abuse
• History of alcohol abuse (4 or greater drinks per day on average)
• Unable to complete MRI scans (no Pacemaker/Defibrillator)
• Known clinically significant abnormalities in B12 or thyroid function tests
• End Stage Renal Disease (ESRD)
• Hemodialysis (HD)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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26 participants in 2 patient groups

AGB101 220 mg, then Placebo

Experimental group

Description:

AGB101 220 mg/day capsule, once daily dosing for 2 weeks. After a 4 week washout, to be followed by Placebo, given as a capsule, once daily dosing for 2 weeks.

Treatment:

Other: Placebo

Drug: AGB101 220 mg

Placebo, then AGB101 220 mg

Experimental group

Description:

Placebo, given as a capsule, once daily for 2 weeks. After a 4 week washout, to be followed by AGB101 220 mg/day capsule, once daily dosing for 2 weeks.

Treatment:

Other: Placebo

Drug: AGB101 220 mg