Brain Imaging in the Diabetes Prevention Program Outcomes Study

Early Phase 1

Terminated

• Conditions: Alzheimer Disease
• Interventions: Drug: 18F-MK-6240; Drug: 11C-PIB

• Registration Number: NCT03757910
• Lead Sponsor: José A. Luchsinger

Brief Summary

This is a cross-sectional pilot study of Alzheimer's disease (AD) brain imaging biomarkers in Diabetes Prevention Program (DPP) outcomes study (DPPOS) participants from the New York City sites (Columbia and Einstein), comparing 10 persons originally randomized to metformin and 10 persons randomized to placebo in DPP. All study procedures will be conducted at Columbia University Irving Medical Center. Eligible participants will receive a PET scans and a brain MRI, which may be conducted in one, two, or three separate visits.

Detailed Description

Hyperinsulinemia is believed to increase the risk of Alzheimer's dementia through both cerebrovascular and A related mechanisms, and this hypothesis has prompted testing strategies related to hyperinsulinemia and diabetes in the prevention and treatment of Alzheimer's dementia.These strategies usually entail improving insulin sensitivity to lower insulin and glucose levels, such as lifestyle (diet and exercise) and metformin, which were effective strategies for preventing diabetes in the DPPOS. There are conflicting data relating metformin with increased AD risk, and this needs to be clarified in DPPOS. Several laboratory and human studies have suggested that metformin increases the risk of Alzheimer's dementia, but this is countered by other studies indicating that it is beneficial. Preliminary data in humans and animals support the beneficial effects of metformin on Alzheimer's dementia risk.

Study Timeline

• Study First Submitted: 2018-11-27
• Study First Submitted QC: 2018-11-27
• Study First Posted: 2018-11-29
• Study Start: 2019-10-01
• Primary Completion: 2023-01-31
• Study Completion: 2023-01-31
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-01
• Last Update Posted: 2024-03-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• Active participants in the Diabetes Prevention Program Outcomes Study (DPPOS) in New York City originally randomized to metformin or placebo
• 60 years and older

Exclusion Criteria

• Known dementia
• Contraindications to magnetic resonance imaging (MRI)
• Contraindications to radio-contrast agents.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DPPOS Exposed to Metformin	18F-MK-6240	DPPOS participants with exposure to metformin will be scanned with 18F-MK-6240 and 11C-PIB.
DPPOS Exposed to Metformin	11C-PIB	DPPOS participants with exposure to metformin will be scanned with 18F-MK-6240 and 11C-PIB.
DPPOS Exposed to Placebo	18F-MK-6240	DPPOS participants with no exposure to metformin but only placebo will be scanned with 18F-MK-6240 and 11C-PIB.
DPPOS Exposed to Placebo	11C-PIB	DPPOS participants with no exposure to metformin but only placebo will be scanned with 18F-MK-6240 and 11C-PIB.

Primary Outcome Measures

Name	Time	Method
Brain Amyloid SUVR	Up to 1 hour post-injection	Whole brain amyloid (11C-PIB) standardized uptake volume ratio (SUVR)
Brain Tau SUVR	Up to 1 hour post-injection	Tau (18F-MK-6240) SUVR in medial and inferior temporal lobes

Secondary Outcome Measures

Name	Time	Method
Hippocampal Cortical Thickness	Up to 1 hour post-injection	Thickness in the hippocampal cortex
White Matter Hyper Intensity Volume	Up to 1 hour post-injection	Volume of brain white matter hyper-intensities

Trial Locations

Locations (1)

Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States