Brain Imaging in the Diabetes Prevention Program Outcomes Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: 18F-MK-6240
* Drug: 11C-PIB


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, Pre-diabetes, Type 2 diabetes, DPPOS