Clinical trial NCT04098666: Metformin in Alzheimer's Dementia Prevention
Official title: Metformin in Alzheimer's Dementia Prevention
Conditions: Mild Cognitive Impairment
Summary: 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 326 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 18 months and have 4 visits: baseline, 6-months, 12-months, and 18-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 18. 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 endpoints are 1) changes in global cognitive performance, measured with the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC); 2) changes in neurodegeneration, ascertained as cortical thickness in areas affected by AD on brain MRI; 3) changes in cerebrovascular disease, ascertained as white matter hyperintensities (WMH) volume on brain MRI; 4) Changes in whole brain amyloid ß (Aß) SUVR and in incident amyloid positivity; 5) Changes in tau SUVR in a composite brain region comprising medial and inferolateral temporal cortex; 6) Changes in plasma AD biomarkers.
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.
Interventions:
description: Placebo tablet identical to metformin, up to 4 tablets a day
name: Placebo oral tablet
other_name: Placebo
type: Drug
description: Metformin extended release 500 mg tablets, up to 4 tablets a day
name: extended release metformin
other_name: Metformin
type: Drug
Study arms:
design_group_description: Extended release metformin 500 mg tablets up to 2,000 mg (4 tablets) a day once at night. The maximum dose will be attempted during a titration period in the first month of the study.
design_group_title: metformin users
design_group_type: Experimental
design_group_description: Placebo tablets identical to extended release metformin 500 mg tablets up to 4 tablets a day once at night. The maximum dose will be attempted during a titration period in the first month of the study.
design_group_title: metformin non-users
design_group_type: Placebo Comparator
Sponsor: Columbia University
Collaborators: Boston University
The University of Texas Southwestern Medical Center
State University of New York at Buffalo
The University of New Mexico
Eastern Virginia Medical School
Medical College of Wisconsin
Stanford University
Pennington Biomedical Research Center
National Institute on Aging
Wake Forest University
University of Kansas Medical Center
The Johns Hopkins University
University of Rochester
University of California, Irvine
Rush University
University of California, Berkeley
Cornell University
University of Texas Health Science Center At San Antonio
SUNY Upstate Medical University
NYU Langone Health
Emory University
University of Washington
Georgetown University
University of Iowa
University of Miami
Drug name mappings:
name: 二甲双胍
lang: CN
name: Metformin
lang: EN