Network-Level Mechanisms for Preclinical Alzheimer's Disease Development

June 30, 2023 updated by: Yang Wang, Medical College of Wisconsin
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert & the Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AGB101 220 mg, then Placebo
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.
Drug: AGB101 220 mg
AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.
Other: Placebo
Placebo, oral capsule given once-daily.
Experimental: Placebo, then AGB101 220 mg
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.
Drug: AGB101 220 mg
AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.
Other: Placebo
Placebo, oral capsule given once-daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional Connectivity Strengths of Neural Networks
Time Frame: 2 weeks after treatment between AGB101 and Placebo
The seed-based functional connectivity strengths of the hippocampus network and the default mode network will be employed to measure the changes between AGB101 and Placebo perturbation. The functional connectivity strengths will be measured with the median of the Pearson cross-correlation coefficients over entire brain regions.
2 weeks after treatment between AGB101 and Placebo

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rey Auditory Verbal Learning Test (AVLT), Delayed Recall Scaled Integer. The Higher is the Better
Time Frame: Placebo vs AGB101 2 weeks after treatment paired t-test
Rey Auditory Verbal Learning Test (AVLT), delayed recall Scaled integer will be employed to measure the episodic memory changes before and after AGB101 treatment. The AVLT score will be recorded as a standard score. The theoretical range: min 50, max 155, the higher the better. The higher the number is, the better the memory. It is an integer number.
Placebo vs AGB101 2 weeks after treatment paired t-test

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical College of Wisconsin

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Yang Wang, PhD, The Medical College of Wisconsin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 11, 2019

Primary Completion (Actual)

March 31, 2021

Study Completion (Actual)

March 31, 2021

Study Registration Dates

First Submitted

February 26, 2018

First Submitted That Met QC Criteria

March 5, 2018

First Posted (Actual)

March 12, 2018

Study Record Updates

Last Update Posted (Actual)

July 3, 2023

Last Update Submitted That Met QC Criteria

June 30, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO00031146
  • R21AG056882-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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