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Network-Level Mechanisms for Preclinical Alzheimer's Disease Development

Primary Purpose

APOE 4

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

AGB101 220 mg

Placebo

About this trial

This is an interventional prevention trial for APOE 4 focused on measuring Healthy, Adult, Normal Memory, APOE 4, Brain, Magnetic Resonance Imaging, MRI, Alzheimer's disease, Hippocampus, Genetic testing, Dementia, AGB101

Eligibility Criteria

55 Years - 75 Years (Adult, Older Adult)All SexesAccepts 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)

Sites / Locations

Froedtert & The Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

AGB101 220 mg, then Placebo

Placebo, then AGB101 220 mg

Arm 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.

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.

Outcomes

Primary Outcome Measures

Functional Connectivity Strengths of Neural Networks

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.

Secondary Outcome Measures

Rey Auditory Verbal Learning Test (AVLT), Delayed Recall Scaled Integer. The Higher is the Better

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.

Full Information

NCT ID

NCT03461861

First Posted

February 26, 2018

Last Updated

June 30, 2023

Sponsor

Medical College of Wisconsin

Collaborators

National Institute on Aging (NIA)

1. Study Identification

Unique Protocol Identification Number

NCT03461861

Brief Title

Network-Level Mechanisms for Preclinical Alzheimer's Disease Development

Official Title

Network-Level Mechanisms for Preclinical Alzheimer's Disease Development

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

April 11, 2019 (Actual)

Primary Completion Date

March 31, 2021 (Actual)

Study Completion Date

March 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Medical College of Wisconsin

Collaborators

National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

APOE 4

Keywords

Healthy, Adult, Normal Memory, APOE 4, Brain, Magnetic Resonance Imaging, MRI, Alzheimer's disease, Hippocampus, Genetic testing, Dementia, AGB101

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

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.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AGB101 220 mg, then Placebo

Arm Type

Experimental

Arm 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.

Arm Title

Placebo, then AGB101 220 mg

Arm Type

Experimental

Arm 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.

Intervention Type

Drug

Intervention Name(s)

AGB101 220 mg

Intervention Description

AGB101 oral dose of 220 mg/day capsule, given as once-daily dosing.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo, oral capsule given once-daily.

Primary Outcome Measure Information:

Title

Functional Connectivity Strengths of Neural Networks

Description

Time Frame

2 weeks after treatment between AGB101 and Placebo

Secondary Outcome Measure Information:

Title

Rey Auditory Verbal Learning Test (AVLT), Delayed Recall Scaled Integer. The Higher is the Better

Description

Time Frame

Placebo vs AGB101 2 weeks after treatment paired t-test

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yang Wang, PhD

Organizational Affiliation

The Medical College of Wisconsin

Official's Role

Principal Investigator

Facility Information:

Facility Name

Froedtert & The Medical College of Wisconsin

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53226

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Citation

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Network-Level Mechanisms for Preclinical Alzheimer's Disease Development

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