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.
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Brain Amyloid SUVR
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 60 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
DPPOS Exposed to Metformin
DPPOS participants with exposure to metformin will be scanned with 18F-MK-6240 and 11C-PIB.
Intervention: 18F-MK-6240 (Drug)
DPPOS Exposed to Metformin
DPPOS participants with exposure to metformin will be scanned with 18F-MK-6240 and 11C-PIB.
Intervention: 11C-PIB (Drug)
DPPOS Exposed to Placebo
DPPOS participants with no exposure to metformin but only placebo will be scanned with 18F-MK-6240 and 11C-PIB.
Intervention: 18F-MK-6240 (Drug)
DPPOS Exposed to Placebo
DPPOS participants with no exposure to metformin but only placebo will be scanned with 18F-MK-6240 and 11C-PIB.
Intervention: 11C-PIB (Drug)
Outcomes
Primary Outcomes
Brain Amyloid SUVR
Time Frame: Up to 1 hour post-injection
Whole brain amyloid (11C-PIB) standardized uptake volume ratio (SUVR)
Brain Tau SUVR
Time Frame: Up to 1 hour post-injection
Tau (18F-MK-6240) SUVR in medial and inferior temporal lobes
Secondary Outcomes
- Hippocampal Cortical Thickness(Up to 1 hour post-injection)
- White Matter Hyper Intensity Volume(Up to 1 hour post-injection)
Investigators
José A. Luchsinger
Professor of Medicine and Epidemiology
Columbia University