What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis (MS) include disease-modifying therapies such as dimethyl fumarate, glatiramer acetate, and metformin (under study). Dimethyl fumarate can cause gastrointestinal issues, flushing, and a decrease in white blood cell count. Glatiramer acetate may lead to injection site reactions, chest pain, and lipoatrophy. Metformin, while primarily used for diabetes, is being studied for MS and is known to cause gastrointestinal disturbances, vitamin B12 deficiency, and lactic acidosis in rare cases. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

FDA-approved treatments for Multiple Sclerosis (MS) primarily include disease-modifying therapies (DMTs) such as interferon beta, glatiramer acetate, and monoclonal antibodies like ocrelizumab and natalizumab. These treatments focus on modulating the immune system to reduce the frequency and severity of MS relapses. While metformin is being studied for its potential benefits in MS due to its effects on glucose metabolism and possibly neuroprotection, there are no current FDA-approved MS treatments that share its primary mechanism of action related to glucose metabolism.

What other types of research exist?

Promising alternatives to Metformin for Multiple Sclerosis patients include Glucagon-like peptide-1 (GLP-1) receptor agonists and Sodium-glucose cotransporter-2 (SGLT2) inhibitors. GLP-1 receptor agonists improve insulin secretion, reduce glucagon secretion, and slow gastric emptying, which can help manage blood glucose levels. SGLT2 inhibitors reduce glucose reabsorption in the kidneys, leading to increased glucose excretion. Both classes of drugs have shown potential benefits in managing type 2 diabetes and may offer metabolic advantages for MS patients.

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Biguanide

Metformin for Progressive Multiple Sclerosis

Phase < 1

Recruiting

Led By Kevin R Patel, MD

Research Sponsored by University of California, Los Angeles

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 30-65

Primary Progressive Multiple Sclerosis or Secondary Progressive Multiple Sclerosis as defined by the 2017 McDonald Criteria

Must not have

Plans to change current disease modifying therapy

Renal dysfunction (GFR < 60)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up between month 0 and month 12

Summary

This trial is testing metformin, a diabetes medication, to see if it can help adults aged 30-65 with progressive multiple sclerosis. The goal is to find out if metformin can reduce inflammation and protect nerve cells, potentially slowing down the disease.

Who is the study for?

This trial is for people aged 30-65 with Progressive Multiple Sclerosis who have been stable on their current MS treatment for at least three months. They must not have had a clinical relapse or new lesions in the past year and should not be using metformin for other conditions, nor have kidney or liver issues, B12 deficiency, heart failure, alcohol abuse, metabolic acidosis, or plans to become pregnant.

What is being tested?

The study is testing the safety of metformin (up to four 500 mg tablets daily) compared to a placebo in treating progressive multiple sclerosis. Participants will continue their usual MS treatments during the trial and either add metformin or a look-alike pill without active medication.

What are the potential side effects?

Potential side effects of metformin include digestive upset like nausea and diarrhea, risk of vitamin B12 deficiency over time, and very rarely a serious condition called lactic acidosis where too much acid builds up in the blood.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 30 and 65 years old.

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My condition is diagnosed as progressive multiple sclerosis according to the 2017 criteria.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I plan to change my current treatment for my condition.

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My kidney function is reduced.

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I am not pregnant, planning to become pregnant, or breastfeeding during the trial.

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I have had a bad reaction to metformin before.

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My condition worsened in the last year.

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I had a bad reaction to metformin.

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I am not taking any medications that interact with metformin.

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I am currently taking metformin for a condition other than diabetes.

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My liver tests are higher than normal.

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I have been diagnosed with congestive heart failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ between month 0 and month 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~between month 0 and month 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and between month 0 and month 12 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

number of patients with adverse events between baseline and conclusion (month 0 and month 12)

number of patients with laboratory abnormalities between baseline and conclusion (month 0 and month 12)

number of patients with new T2 lesions on MRI from baseline to conclusion (month 0 and month 12)

Secondary study objectives

a reduction in localized cortical thinning on brain MRI between baseline and conclusion (month 0 and month 12)

a reduction in thalamic atrophy on brain MRI between baseline and conclusion (month 0 and month 12)

Other study objectives

decrease in number of phase rimmed lesions between baseline and conclusion (month 0 and month 12)

decrease in plasma neurofilament light chain levels between baseline and conclusion (month 0 and month 12)

improvement in CVLT-II score between baseline and conclusion (month 0 and month 12)

+3 more

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Metformin TreatmentExperimental Treatment1 Intervention

Metformin 500 mg tablets up to 2,000 mg (4 tablets) a day divided into two doses. Patients will start on 500 mg Qday and a titration to maximum dose will be attempted during the first 30 day period of the study.

Group II: Placebo TreatmentPlacebo Group1 Intervention

Placebo tablets identical to metformin 500 mg tablets divided into two doses. Patients will be started on 1 tablet a day and a titration to maximum dose (4 tablets) will be attempted during the first 30 day period of the study.

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Multiple Sclerosis (MS) include disease-modifying therapies (DMTs) such as dimethyl fumarate, glatiramer acetate, and metformin. Dimethyl fumarate works by activating the Nrf2 pathway, which reduces oxidative stress and inflammation. Glatiramer acetate mimics myelin basic protein, distracting the immune system from attacking myelin. Metformin, although primarily a diabetes medication, has shown potential in MS by increasing regulatory T cells and reducing inflammation. These mechanisms are crucial for MS patients as they help to reduce relapse rates, slow disease progression, and manage symptoms by targeting the underlying immune dysfunction and neurodegeneration characteristic of MS.

Dietary Interventions in Multiple Sclerosis: Development and Pilot-Testing of an Evidence Based Patient Education Program.Immunologic Effects of Metformin and Pioglitazone Treatment on Metabolic Syndrome and Multiple Sclerosis.Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice.