Clinical trial NCT03461861: Network-Level Mechanisms for Preclinical Alzheimer's Disease Development
Official title: Network-Level Mechanisms for Preclinical Alzheimer's Disease Development
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: APOE 4
Keywords: Healthy
Adult
Normal Memory
APOE 4
Brain
Magnetic Resonance Imaging
MRI
Alzheimer's disease
Hippocampus
Genetic testing
Dementia
AGB101
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2018-03-12
Enrollment: 26
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a randomized, double-blind, placebo-controlled crossover study in which a low dose of AGB101 (220mg QD) or placebo will be administered to 50 healthy 55-75-year-old subjects, with the order of treatments counterbalanced in a within-subject crossover design.
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Functional Connectivity Strengths of Neural Networks
timeFrame: 2 weeks after treatment between AGB101 and Placebo
Secondary outcomes:
measure: Rey Auditory Verbal Learning Test (AVLT), Delayed Recall Scaled Integer. The Higher is the Better
timeFrame: Placebo vs AGB101 2 weeks after treatment paired t-test
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Froedtert & The Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: The Medical College of Wisconsin
name: Yang Wang, PhD
role: PRINCIPAL_INVESTIGATOR
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