Metformin for Multiple Sclerosis

Recruiting at 1 trial location

Overseen By Shamashtika Thilagaratnam, BSc

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The Hospital for Sick Children

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3-9 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the feasibility of starting metformin at different times. Participants will take metformin for several months. Metformin helps lower blood sugar levels by reducing sugar release from the liver and improving insulin response. The likely target group is people with type 2 diabetes. Metformin has been shown to be effective in improving glycemic control in type 2 diabetes and has a history of being used in various dosages and combinations to manage blood sugar levels.

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 on insulin, certain drugs that interact with metformin, or other remyelinating therapies. Your current medications will be reviewed by the trial investigators to ensure they don't interfere with metformin.

Is metformin safe for use in humans?

Metformin, commonly used for diabetes, has been studied for safety in various conditions, including as an additional treatment for multiple sclerosis. It is generally considered safe for human use, but like any medication, it may have side effects, so it's important to discuss with a healthcare provider. ^{1 2 3 4 5}

How is the drug Metformin unique in treating multiple sclerosis?

Metformin is unique in treating multiple sclerosis because it is traditionally used for managing type 2 diabetes by improving insulin sensitivity, which is different from typical MS treatments like glatiramer acetate that focus on modulating the immune system. This novel approach suggests a potential new mechanism of action for MS treatment. ^{5 6 7 8 9}

Research Team

E. Ann Yeh, MA, MD, FRCPC, Dip ABPN

Principal Investigator

The Hospital for Sick Children

Eligibility Criteria

Inclusion Criteria

The thickness of a specific part of your eye, called the Retinal Nerve Fiber Layer, must be at least 60 micrometers on a special eye scan taken before the trial starts.

Age 10 year to 25 years and 11 months

Stable immunomodulatory therapy - no switch or planned switch in > 6 months and no change in doses in 30 days prior to screening

Exclusion Criteria

You are already taking metformin.

Your lactate levels are higher than they should be.

You are currently taking insulin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin or placebo for a minimum of 3 months and a maximum of 9 months, depending on randomization

3-9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Metformin
• Placebo

Participant Groups

Group I: Group C Experimental Treatment 2 Interventions

Placebo for 9 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day. Metformin for 3 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.

Group II: Group B Experimental Treatment 2 Interventions

Placebo for 6 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day. Metformin for 6 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.

Group III: Group A Experimental Treatment 2 Interventions

Placebo for 3 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day. Metformin for 9 months at dose of 500 mg/m2/day po (to be rounded) given in 1 or 2 divided doses for one week and if there are no side effects increased to 1000 mg/m2/day po given in 2 divided doses up to a maximum dose of 2000 mg/day.

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?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Ontario Institute for Regenerative Medicine

Collaborator

Trials

2

Recruited

60+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Stem Cell Network

Collaborator

Trials

9

Recruited

600+

Multiple Sclerosis Society of Canada

Collaborator

Trials

17

Recruited

990+

Queen's University

Collaborator

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Findings from Research

In a study involving 80 patients with relapsing-remitting multiple sclerosis, adding metformin to interferon beta 1a treatment showed a significant reduction in malondialdehyde (MDA), a marker of oxidative stress, suggesting a potential benefit in managing oxidative stress in MS patients.

However, there were no statistically significant improvements in immunological markers, MRI results, or clinical outcomes (measured by the Expanded Disability Status Scale) between the metformin and control groups after 6 months, indicating that while metformin may affect oxidative stress, it does not enhance overall treatment efficacy in RRMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of metformin use on the outcomes of relapse-remitting multiple sclerosis patients receiving interferon beta 1a: an exploratory prospective phase II open-label randomized controlled trial. Abdelgaied, MY., Rashad, MH., El-Tayebi, HM., et al.[2023]

Glatiramer acetate (GA) has been safely used for over 20 years in treating relapsing-remitting multiple sclerosis (MS), showing a 30% reduction in annual relapse rates and decreased brain lesion activity, with no new safety concerns reported.

GA's unique anti-inflammatory and neuroprotective mechanisms help slow brain atrophy and delay the onset of clinically definite MS, making early treatment more effective, while also being safe for use during pregnancy and in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis. Boster, AL., Ford, CC., Neudorfer, O., et al.[2022]

The review highlights that while older MS treatments like glatiramer acetate and interferon beta have a proven safety record, newer therapies may offer greater efficacy but come with potentially more severe risks that are not fully understood.

It emphasizes the importance of careful risk-benefit evaluations and monitoring for adverse events associated with all approved MS therapies, including both established and recently approved medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Requirement for safety monitoring for approved multiple sclerosis therapies: an overview. Rommer, PS., Zettl, UK., Kieseier, B., et al.[2021]

In a study of 194 multiple sclerosis patients over one year, glatiramer acetate (GA) significantly reduced the annualized relapse rate (ARR) for both drug-naïve and switcher patients compared to the previous 24 months, indicating its effectiveness in real-world clinical practice.

The safety profile of GA was favorable, with no new unexpected adverse events reported, and it was often prescribed due to concerns about side effects from other treatments, such as interferons, and considerations like pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of glatiramer acetate between 2010-2015: effectiveness, safety and reasons to start GA as first or second line treatment in Swiss multiple sclerosis patients. Zecca, C., Disanto, G., Sacco, R., et al.[2020]

Glatiramer acetate (GA) has been an approved treatment for relapsing-remitting multiple sclerosis (MS) since 1996 and is one of the first-line therapies for this condition.

Recent studies suggest that GA works as an immunomodulatory agent by influencing immune responses, which is based on its development from the animal model of MS known as experimental autoimmune encephalomyelitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glatiramer acetate treatment of multiple sclerosis: an immunological perspective. Racke, MK., Lovett-Racke, AE.[2015]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The impact of metformin use on the outcomes of relapse-remitting multiple sclerosis patients receiving interferon beta 1a: an exploratory prospective phase II open-label randomized controlled trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Requirement for safety monitoring for approved multiple sclerosis therapies: an overview. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Pregnancy, Fetal, and Infant Outcomes Following Maternal Exposure to Glatiramer Acetate During Pregnancy and Breastfeeding. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Use of glatiramer acetate between 2010-2015: effectiveness, safety and reasons to start GA as first or second line treatment in Swiss multiple sclerosis patients. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Glatiramer acetate for the treatment of multiple sclerosis. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Glatiramer acetate treatment of multiple sclerosis: an immunological perspective. [2015]

8. Germany pubmed.ncbi.nlm.nih.gov

Classical immunomodulatory therapy in multiple sclerosis: how it acts, how it works. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Glatiramer acetate in multiple sclerosis. [2015]