MAP

(MAP Trial)

Recruiting in Palo Alto (17 mi)

+22 other locations

Overseen by José A Luchsinger, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Waitlist Available

Sponsor: Columbia University

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Research Team

José A Luchsinger, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for men and women aged 55-90 with early or late mild cognitive impairment (MCI), specifically those who have memory concerns but not a diagnosis of Alzheimer's. Participants must not have diabetes, be overweight or obese, and able to attend study visits or available by phone. They should also have sufficient vision and hearing for tests.

Inclusion Criteria

Study Partner Inclusion Criteria: The study partner can provide an independent evaluation of functioning for a person enrolled in the MAP study as a participant. The study partner agrees to attend study visits with the MAP participant or be available by telephone.

My education level is between 8-15 years.

My education level is between 0-7 years and my score is between 3-6.

Exclusion Criteria

You cannot participate in the study if you have a low body mass index, kidney disease with an estimated glomerular filtration rate of less than 45 mL/min, liver disease other than non-fatty liver disease or class III or IV congestive heart failure, moderate to severe depression, dementia, or a history of intolerance to metformin. You also cannot participate if you have had a cerebrovascular accident with residual neurological deficits, neurologic diseases associated with neurological deficits, active cancer or a history of cancer in the last two years (except for certain types of skin cancer), uncontrolled hypertension, or are planning to move to another city or state within the next 24 months. Additionally, you cannot participate if you have a known history of diabetes or if it is discovered during screening using HbA1c criteria. You also cannot participate if you are taking certain medications or treatments, such as aducanumab or amyloid modifying treatments for Alzheimer's disease, or if you are pregnant or planning to become pregnant. Finally, you cannot participate if you are unable to undergo phlebotomy.

Have you noticed changes in your memory?

I have never been diagnosed with Alzheimer's disease.

Treatment Details

Interventions

• Metformin (Biguanide)

Trial Overview The MAP trial is testing extended-release metformin against a placebo in individuals without diabetes who are at risk for Alzheimer's. Over 18 months, participants will take increasing doses of the drug/placebo while undergoing neuropsychological tests, physical exams, brain scans, and bloodwork to monitor changes in memory function.

Participant Groups

Group I: metformin users Experimental Treatment 1 Intervention

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.

Group II: metformin non-users Placebo Group 1 Intervention

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.

Metformin is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Dr. Katrina Armstrong

Columbia University

Chief Executive Officer

MD from Johns Hopkins University, MS in Epidemiology from Harvard School of Public Health

Dr. Katrina Armstrong

Columbia University

Chief Medical Officer

MD from Harvard Medical School

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

Kevin Koch

University of Rochester

Chief Executive Officer since 2020

PhD in Organic Chemistry from the University of Rochester

Brian Druker

University of Rochester

Chief Medical Officer since 2015

MD from Harvard Medical School

Georgetown University

Collaborator

Trials

355

Recruited

142,000+

Dr. Ivica Labuda

Georgetown University

Chief Executive Officer since 2022

PhD in Biochemistry and Molecular & Cellular Biology from Slovak Academy of Sciences, University of Graz, and Rutgers University

Dr. Richard Ascione

Georgetown University

Chief Medical Officer since 2023

MD from Georgetown University Medical School

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Dr. Alec C. Kimmelman

NYU Langone Health

Chief Executive Officer

MD and PhD from Mount Sinai School of Medicine

Dr. Nicole M. Adler

NYU Langone Health

Chief Medical Officer since 2023

MD

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Dr. Timothy H. Dellit

University of Washington

Chief Executive Officer since 2023

MD from University of Washington

Dr. Anneliese Schleyer

University of Washington

Chief Medical Officer since 2023

MD, MHA

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

Matthew DeLisa

Cornell University

Chief Executive Officer since 2019

PhD in Chemical Engineering from Cornell University

Tami Magnus

Cornell University

Chief Medical Officer since 2015

MBA from Binghamton University

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

University at Buffalo

Collaborator

Trials

139

Recruited

105,000+

Satish K. Tripathi

University at Buffalo

Chief Executive Officer since 2011

PhD in Computer Science from University of Toronto

Brian M. Parker

University at Buffalo

Chief Medical Officer since 2021

MD from University of Pennsylvania

University of Cincinnati

Collaborator

Trials

442

Recruited

639,000+

Dr. Greg Postel

University of Cincinnati

Chief Medical Officer since 2020

MD from Indiana University School of Medicine

Dr. Neville G. Pinto

University of Cincinnati

Chief Executive Officer since 2017

PhD in Chemistry from the University of Virginia