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

• ClinicalTrials.gov Identifier: NCT03757910
• Recruitment Status: Enrolling by invitation
• First Posted: November 29, 2018
• Last Update Posted: July 9, 2021
• Sponsor: José A. Luchsinger
• Collaborators: Albert Einstein College of Medicine; George Washington University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): José A. Luchsinger, Columbia University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: 18F-MK-6240; Drug: 11C-PIB	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: 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.
• Actual Study Start Date: October 1, 2019
• Estimated Primary Completion Date: January 31, 2022
• Estimated Study Completion Date: January 31, 2022

Arms and Interventions

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 Name: 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 Name: 11C-Pittsburgh Compound B

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Hippocampal Cortical Thickness [ Time Frame: Up to 1 hour post-injection ]
   Thickness in the hippocampal cortex
2. White Matter Hyper Intensity Volume [ Time Frame: Up to 1 hour post-injection ]
   Volume of brain white matter hyper-intensities

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

Albert Einstein College of Medicine

New York, New York, United States, 10461

Sponsors and Collaborators

José A. Luchsinger

Albert Einstein College of Medicine

George Washington University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: F. X. Pi-Sunyer, MD; Columbia University

More Information

• Responsible Party: José A. Luchsinger, Professor of Medicine and Epidemiology, Columbia University
• ClinicalTrials.gov Identifier: NCT03757910
• Other Study ID Numbers: AAAS1176; 3U01DK048404-25S1 ( U.S. NIH Grant/Contract )
• First Posted: November 29, 2018
• Last Update Posted: July 9, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by José A. Luchsinger, Columbia University:

Metformin; Pre-diabetes; Type 2 diabetes; DPPOS

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Corticosterone; Anti-Inflammatory Agents