Metformin to activate neural progenitor cells in children and young adults with MS
Official title: A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children and Young Adults With Multiple Sclerosis
Run by The Hospital for Sick Children · NCT04121468 · Data updated 2026-11-12
This trial will try giving metformin or placebo to children and young adults with MS to see if metformin helps the brain cells that repair myelin.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Ages | 10 Years to 25 Years |
| Sex | All |
| Enrollment | 20 (estimated) |
| Sponsor | The Hospital for Sick Children Academic / other |
| Locations | 1 site (Toronto, Ontario) |
| Status | Recruiting |
| Started | February 24, 2020 |
| Main results expected | March 2027 |
| Study ends | October 2027 |
| Registry record updated | September 23, 2025 |
| Trial ID | NCT04121468 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are people aged 10 to 25 years 11 months with MS and prior anterior visual pathway involvement (optic neuritis or an acute demyelinating event >6 months prior), with electrophysiological or OCT evidence of demyelination (VEP latency delay or RNFL thinning ≥10 µm inter-eye difference or RNFL <90 µm) but RNFL ≥60 µm, EDSS 0–6.0, stable disease-modifying therapy for 6 months if applicable, and no significant renal or liver abnormalities with sufficient English comprehension for testing.
✕Probably not a fit
People with advanced disability (EDSS >6), very thin RNFL below the required threshold (<60 µm), recent relapses or recent changes in MS therapy, or significant renal or liver impairment are unlikely to qualify and therefore would not be expected to benefit from this trial.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This is a double-blind, randomized multiple-baseline feasibility trial in participants aged 10 to 25 that staggers the start of daily metformin (or placebo) at one of three randomized timepoints over a 12-month follow-up. Each participant will receive metformin for at least 3 months and up to 9 months, with clinical and eye-based measures (like visual evoked potentials and OCT RNFL thickness) used to track change. The design focuses on safety, tolerability, and signals of remyelination in the anterior visual pathway in youth with prior optic pathway involvement. The trial is Phase I/II and conducted at a single pediatric center with external academic collaborators.
Why it matters
Potential benefit: If successful, metformin could help stimulate remyelination and lead to measurable improvements in visual nerve measures and potentially clinical function in young people with MS.
How similar studies have gone: Preclinical studies in animals show metformin can boost neural precursor activity and promote remyelination, but clinical evidence for this approach in MS is very limited so human efficacy remains unproven.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patients with a history of MS with anterior visual pathway involvement and longer than 6 months after presentation with ON or an acute demyelinating event/relapse * Age 10 year to 25 years and 11 months * Latency delay \> 115 milliseconds on baseline full-field transient pattern reversal VEP in at least one eye (electrophysiological evidence of demyelination) or \> 10 milliseconds difference between eyes, or Retinal Nerve Fiber Layer (RNFL) thickness on OCT of \< 90 µm in at least one eye or an inter-eye difference in the RNFL of 10 µm or more * Retinal Nerve Fiber Layer (RNFL) Thickness on baseline OCT ≥60 µm * If on an MS disease-modifying therapy, no changes in the therapeutic agent or dosing in the 6 months prior to study initiation * No significant renal or liver abnormalities * Expanded Disability Status Scale (EDSS) 0-6.0 (inclusive) * Has either English as his or her native language or English comprehension needed to complete the neuropsychological testing * Meet criteria for adequate organ function requirements as described below: Adequate renal function defined as: Creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 70 mL/min/1.73 m2 or serum creatinine based on age/gender as follows: Range Serum Creatinine Level (µmol/L): Age 5 to \<12 years (male)=25-50, Age 5 to \<12 years (female)=25-50; Age 12 to \<15 years (male)=37-67, Age 12 to \<15 years (female)=37-67; Age 15 to \<19 years (male)=51-89, Age 15 to \<19 years (female)=40-69; Age ≥19 years (male)=58-110; Age ≥19 years (female)=46-92 Adequate liver function defined as: Total bilirubin \< 1.5 x upper limit of normal (ULN) for age SGOT (AST) or SGPT (ALT) \< 1.5 x upper limit of normal (ULN) for age Exclusion Criteria: * A history of retinal pathology (major ophthalmologic disease / concomitant ophthalmologic disorders) * Unstable and/or insulin-dependent (Type 1) diabetes, metabolic acidosis and/or lactic acidosis * History of unexplained hypoglycemia (\<2.8 mmol/L) * Already on metformin * Concomitant use of any other putative remyelinating therapy as determined by the Principal/Qualified Investigator * Treatment for an acute attack with corticosteroids within 30 days prior to screening / relapse within 30 days prior to screening * Concomitant use of insulin * Concomitant use of any drugs that are listed to have drug-drug interactions with metformin (i.e. calcium channel blockers, diuretics, etc.) as determined by Principal/Qualified Investigator * Lactate levels \> 1.5x upper limit of normal * Pregnancy
Where it's running
-
The Hospital for Sick Children
Toronto, Ontario, Canada Recruiting
Study contacts
- Principal investigator: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN — The Hospital for Sick Children
- Study coordinator: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN
- Email: ann.yeh@sickkids.ca
- Phone: 416-813-7353
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.