Metformin for Multiple Sclerosis

Recruiting at 1 trial location

Overseen By Brenna Wong

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The Hospital for Sick Children

Must not be taking: Insulin, Corticosteroids

Disqualifiers: Retinal pathology, Diabetes, Pregnancy, others

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

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether metformin, a medication commonly used for diabetes, can help treat multiple sclerosis (MS), with a specific focus on vision problems related to the disease. Participants will take metformin at different times during the study to assess its impact on MS symptoms. The trial seeks individuals with MS who have experienced vision issues for more than six months and have not recently changed their MS treatment plan. As a Phase 1, Phase 2 trial, this research aims to understand how metformin works in people and measure its effectiveness in treating MS-related vision problems.

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

Research shows that metformin is usually well-tolerated by patients. Studies on its use for multiple sclerosis (MS) focus on safety, such as the incidence of side effects or unusual lab results. Although specific results from these studies are not yet available, researchers are actively examining these safety issues.

The FDA has already approved metformin for treating type 2 diabetes, indicating its safety for general use. However, using it for MS is new, so current trials are assessing how well patients tolerate it in this context. Overall, metformin's existing approval for other uses and the emphasis on safety in ongoing research provide some reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Researchers are excited about using Metformin for multiple sclerosis (MS) because it offers a unique approach compared to current treatments. Most MS treatments are focused on modulating or suppressing the immune system, like interferons or monoclonal antibodies. However, Metformin, a drug traditionally used for diabetes, may work differently by potentially restoring energy balance and promoting nerve repair. This could not only provide a new mechanism for addressing MS but also offer a treatment option with a well-known safety profile from its long-term use in diabetes.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

Research has shown that metformin, a common diabetes drug, might help treat multiple sclerosis (MS). Studies have found that metformin can reduce inflammation and protect nerve cells, which is crucial for people with MS. Some research even suggests it might repair brain damage caused by MS. In one study, metformin, when combined with another drug, helped nerve cells regrow their protective coating, a process called remyelination. Although more research is needed, early results are promising for using metformin as a treatment for MS. Participants in this trial will receive metformin for varying durations to evaluate its effectiveness in treating MS. ^{1 2 6 7 8}

Who Is on the Research Team?

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

Principal Investigator

The Hospital for Sick Children

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 10 to 25 years with Multiple Sclerosis who have stable immunomodulatory therapy, no severe kidney or liver issues, and specific visual and neurological criteria. It excludes those already on metformin, with certain metabolic conditions, unstable diabetes, pregnancy, severe eye prescriptions or recent corticosteroid treatment.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Metformin
• Placebo

Trial Overview The study tests Metformin's effect on neural progenitor cells in MS patients by starting treatment at different points over a year. Participants will take either Metformin or a placebo daily for 3 to 9 months to assess feasibility.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11046490/

A metformin add-on clinical study in multiple sclerosis to ... Our study aims to provide evidence for the efficacy of metformin specifically in PMS patients, by focusing on both clinical and cost-related outcome measures.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7503488/

Metformin as a Potential Agent in the Treatment of Multiple ... Hence, this review examines the potential favourable effects of metformin in the course of MS, its role in preventing inflammation and endothelial dysfunction, ...

3. cam.ac.uk cam.ac.uk/research/news/common-diabetes-drug-and-antihistamine-could-together-repair-multiple-sclerosis-damage-trial-finds

Diabetes drug and antihistamine could together repair ... Diabetes drug and antihistamine could together repair multiple sclerosis damage, trial finds. Dr Nick Cunniffe running a 'visual evoked ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05349474

Metformin Treatment in Progressive Multiple Sclerosis Exploratory outcomes include 1) Decrease in plasma neurofilament light chain levels, 2) Reginal nerve fiber layer preservation on OCT, 3) Ganglion cell inner ...

5. practicalneurology.com practicalneurology.com/news/evidence-of-remyelination-seen-in-people-with-ms-receiving-combination-therapy/2483873/

Evidence of Remyelination Seen in People with MS Receiving ... The data demonstrated statistically significant improvements in biomarkers of remyelination associated with the combined therapy, although there ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38070031/

The impact of metformin use on the outcomes of relapse ... We aimed to investigate the efficacy and safety of metformin as an adjuvant therapy to interferon beta 1a (IFNβ-1a) in relapsing-remitting multiple sclerosis ( ...

7. fondation-charcot.org fondation-charcot.org/en/recherche/publications/metformin-add-on-clinical-study-multiple-sclerosis

A metformin add-on clinical study in multiple sclerosis to ... Secondary outcome measures include change in neurological disability (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities ...

8. mssociety.org.uk mssociety.org.uk/research/explore-our-research/emerging-research-and-treatments/explore-treatments-in-trials/metformin

Metformin This is a small safety trial with 30 people aged 10 - 25 years old. Results are expected in 2023.