MAP

(MAP Trial)

Not currently recruiting at 23 trial locations

Overseen By Sara Espinoza, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2 & 3

Sponsor: Columbia University

Must not be taking: Diabetes medications, Benzodiazepines, Narcotics, Amyloid treatments

Disqualifiers: Diabetes, Liver disease, Depression, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin, a medication commonly used for diabetes, can aid memory and thinking problems in individuals with early or late mild cognitive impairment (MCI) related to Alzheimer's. Participants will receive either metformin or a placebo (a pill with no active medicine) to determine if metformin enhances memory and brain health. Individuals with memory issues, but not full-blown Alzheimer's or diabetes, might be suitable for this trial. As a Phase 2 trial, this research measures metformin's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using medications for diabetes or those that might cause cognitive impairment. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that metformin is generally safe for use. It is a common drug for treating type 2 diabetes and has a strong safety record. Studies have found that long-term use of metformin is safe and might even reduce the risk of Alzheimer's disease. In previous studies, people taking metformin did not experience more side effects than those who did not take it.

Some individuals might experience mild side effects like an upset stomach, but these usually improve over time. The well-known safety of this medication makes it a promising option for new uses, such as preventing Alzheimer's disease. As this trial progresses, it will provide more information about metformin's safety in individuals with mild memory problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Metformin is unique for Alzheimer's because it's primarily a diabetes medication that researchers believe could have neuroprotective effects. Unlike standard Alzheimer's treatments like donepezil or memantine, which focus on managing symptoms by targeting neurotransmitter activity, metformin might work by influencing the brain's energy metabolism and reducing inflammation. Researchers are excited because this could mean a novel approach to slowing disease progression by addressing underlying biological processes rather than just alleviating symptoms.

What evidence suggests that metformin might be an effective treatment for Alzheimer's disease?

Research has shown that metformin might help prevent or slow memory and thinking problems in Alzheimer's disease. In this trial, participants will be divided into two groups: metformin users and non-users. Studies have found that people taking metformin have a lower chance of developing dementia. One study discovered that metformin can reduce amyloid-beta, a protein linked to Alzheimer's, in the brain. Observational studies also suggest that metformin users have some protection against dementia. These findings indicate that metformin could benefit people with memory and thinking issues related to Alzheimer's. ^{1 3 4 6 7}

Who Is on the Research Team?

José A Luchsinger, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Telephone pre-screening and in-person screening

Titration

Participants undergo a 30-day titration period where the metformin/placebo dose is increased from 500 mg a day to a maximum of 2,000 mg a day

4 weeks

In-person visits every 10 days

Treatment

Participants receive the study medication or placebo for 18 months with regular assessments

18 months

Baseline, 6-month, 12-month, and 18-month visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Follow-up brain MRI and PET scans for participants who had baseline imaging

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

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+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

Georgetown University

Collaborator

Trials

355

Recruited

142,000+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Cornell University

Collaborator

Trials

179

Recruited

14,090,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

University at Buffalo

Collaborator

Trials

139

Recruited

105,000+

University of Cincinnati

Collaborator

Trials

442

Recruited

639,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724001596

Metformin in the Prevention of Alzheimer's Disease and ... Clinical outcomes. The following are examples of studies showing an association of metformin use with lower risk of cognitive impairment and dementia. In a ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40434891/

Metformin in Alzheimer Dementia Prevention (MAP) Conclusion: Observational studies and pilot trials suggest that metformin may help prevent cognitive decline in neurodegenerative disorders. This clinical trial ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12183985/

Comparative efficacy and safety of antidiabetic agents in ... In terms of reducing Aβ deposition, metformin ranked highest in effectiveness, with the highest SUCRA score (84.6), followed by high-dose ...

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70147

Long‐term metformin use for Alzheimer's disease prevention? The study by Zheng et al. is among a growing number of epidemiological studies reporting a protective effect of metformin on dementia risk, ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2810994

Metformin Cessation and Dementia Incidence | Neurology Previous randomized clinical trials found that metformin treatment improved cognition and lowered dementia risk in people with type 2 diabetes, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39422959/

Metformin as a Potential Prevention Strategy for ... Objective: This review seeks to summarize findings from studies examining the association of metformin with AD/ADRD related outcomes. Methods: This is a ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/66/NCT04098666/Prot_000.pdf

Metformin in Alzheimer's dementia Prevention (MAP) The Alzheimer's Disease Centers' Uniform Data Set (UDS): The. Neuropsychological Test Battery. Alzheimer disease and associated disorders.