MAP will be a multisite phase II/III 1:1 randomized controlled trial (RCT) of long acting
metformin (reduced mass Glucophage XR) vs. matching placebo in 370 men and women with early
and late aMCI, without diabetes, not treated with metformin, overweight or obese, aged 55
years to 90 years. The RCT will last 24 months and have 5 visits: baseline, 6-months,
12-months, 18-months, and 24-months. The RCT will be preceded by a screening phase followed
by randomization and a titration period in which drug/placebo will be titrated from 500 mg a
day (one tablet) to 2,000 mg a day (4 tablets), in increments of 500 mg (one tablet) every 10
days. Participants will remain in the RCT on the tolerated dose, and included in analyses on
an intent to treat basis. We expect the attrition rate to be 10%/year. Neuropsychological
battery, clinical interviews, physical exam, and phlebotomy will be conducted at baseline and
every 6 months. Brain MRI will be conducted in approximately half of the participants (186)
twice, at baseline, and after the last study visit at month 24. We will also conduct brain
amyloid Positron Emission Tomography (PET) using 18F-Florbetaben, and tau PET using
18F-MK6240 in half of the participants at baseline and end of the RCT. The primary clinical
outcome of the study will be changes in the Free and Cued Selective Reminding Test. The
secondary clinical outcome will be changes in the Alzheimer's Disease Cooperative Study
Preclinical Alzheimer's Cognitive Composite. Secondary subclinical outcomes will be changes
in cortical thickness AD signature areas, changes in white matter hyperintensity volume,
changes in brain amyloid burden, changes in brain tau burden, and changes in plasma
biomarkers of amyloid, tau, and neurodegeneration. The data coordinating center and Imaging
Core is located at John Hopkins University. The PET coordinating center is located at
UC-Berkeley. The Clinical Coordinating and Monitoring Center and the central laboratory will
be located at Columbia. The Research pharmacy function will be shared by the University of
Rochester, which will dispense randomization kits, and the University of Iowa, which will
receive bulk metformin and identical matching placebo from EMD Serono.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Columbia University
Collaborators:
Boston University Emory University Georgetown University Johns Hopkins University Louisiana State University Health Sciences Center in New Orleans National Institute on Aging (NIA) NYU Langone Health Pennington Biomedical Research Center Rush University University of California, Berkeley University of Iowa University of Miami University of Rochester Wake Forest University Weill Medical College of Cornell University