Metformin in Alzheimer's Dementia Prevention (NCT04098666) | Clinical Trial Compass
Active — Not RecruitingPhase 2/3
Metformin in Alzheimer's Dementia Prevention
United States326 participantsStarted 2021-03-22
Plain-language summary
MAP will be a multi-center phase 2/3 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.
Who can participate
Age range
55 Years – 90 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
Diagnosis of aMCI: in general, the diagnosis of aMCI follows the definition in the 2011 National Institute on Aging (NIA)/ Alzheimer's association (AA) guidelines, without biomarkers. Participants must have:
* Subjective memory concerns reported by participant, study partner, or clinician.
* A mini-mental state exam between ≥ 22 for subjects with more than 8 years of education. For subjects with less than 8 years of education, a MMSE ≥ 20 will be allowed.
* Clinical Dementia Rating = 0.5. The memory box score must be at least 0.5. Information from the formal University of Washington CDR instrument, report by the participant of subjective cognitive complaints, and findings from the screening neuropsychological battery, can be used for this determination by the investigative team. For example, the University of Washington CDR can be 0, but the CDR memory box score can be deemed to be 0.5 based on cognitive complaints at screening and meeting the MCI neuropsychological criteria.
* General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit.
* Abnormal memory function documented by scoring within the education adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised.
* For early MCI:
* 9-11 for 16 or more years of education
* 5-9 for 8-15 years of …
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial is already in the active phase and not recruiting new participants — does that mean there's no way for me to join it, or are there related studies testing metformin for mild cognitive impairment that I could still be considered for?
2Since this is a Phase 2/3 trial, what do we currently know about whether metformin is safe for someone with my specific health profile, especially since it's a diabetes medication being tested in people without diabetes?
3The trial measures memory using something called the Free and Cued Selective Reminding Test — can you explain what that test actually evaluates, and whether my own memory test results suggest I might benefit from the kind of intervention this study is exploring?
4Metformin is already an approved drug for type 2 diabetes, so is there any scenario where my doctor could consider prescribing it off-label for my mild cognitive impairment now, rather than waiting for trial results, and what are the risks of doing that?
5Given that this trial isn't enrolling anymore, what other options — whether standard treatments, lifestyle interventions, or other clinical trials — should we be looking at to try to slow the progression of my mild cognitive impairment?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.