Brain Imaging in the Diabetes Prevention Program Outcomes Study (DPPOS-Brain)

Amyloid Brain Positron Emission Tomography (PET) Imaging With 11C-PIB and Tau PET Imaging With 18F-MK-6240 in the Diabetes Prevention Program Outcomes Study.

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.

Study Overview

• Status: Terminated
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: 18F-MK-6240; Drug: 11C-PIB

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 Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DPPOS Exposed to Metformin; DPPOS participants with exposure to metformin will be scanned with 18F-MK-6240 and 11C-PIB.	Drug: 18F-MK-6240; This radiotracer will be used to detect Tau.The injected activity will equal 5 millicuries (mCi).; Drug: 11C-PIB; This radiotracer will be used to detect amyloid. Participants will be injected with an intravenous bolus of up to 5-15 mCi.; Other Names: 11C-Pittsburgh Compound B
Active Comparator: DPPOS Exposed to Placebo; DPPOS participants with no exposure to metformin but only placebo will be scanned with 18F-MK-6240 and 11C-PIB.	Drug: 18F-MK-6240; This radiotracer will be used to detect Tau.The injected activity will equal 5 millicuries (mCi).; Drug: 11C-PIB; This radiotracer will be used to detect amyloid. Participants will be injected with an intravenous bolus of up to 5-15 mCi.; Other Names: 11C-Pittsburgh Compound B

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: José A. Luchsinger
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Albert Einstein College of Medicine; George Washington University
• Investigators: Principal Investigator: Jose A. Luchsinger, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Type 2 diabetes; Metformin; Pre-diabetes; DPPOS
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Anti-Inflammatory Agents; Corticosterone
• Other Study ID Numbers: AAAS1176; 3U01DK048404-25S1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No