Recruiting
Phase 1
Phase 2

Metformin

Sponsor:

The Hospital for Sick Children

Code:

NCT04121468

Conditions

Multiple Sclerosis (MS)

Eligibility Criteria

Sex: All

Age: 10 - 25

Healthy Volunteers: Not accepted

Interventions

Metformin

Placebo

Study Details

Brief summary:

A randomized multiple baseline feasibility trial where participants will start taking metformin at one of 3 randomly determined points (3-months, 6-months or 9 months) during the 12-month trial. All subjects will be on a daily dose of metformin for a minimum of 3 months and a maximum of 9 months.

Conditions

Multiple Sclerosis (MS)

Study ID

NCT04121468

Start date

Feb 24, 2020

Status verified date

Sep, 2025

Completion date

Oct, 2027

Anticipated

Primary completion date

Mar, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 10 - 25

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Group A

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.

other: Group B

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.

other: Group C

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.

Interventions

Metformin

Each tablet contains 500mg of metformin hydrochloride

Placebo

Each tablet contains no active drug ingredient

Primary outcome measure

  • Number of patients with adverse events (safety and tolerability) [ Time Frame: 3 years ]
  • Number of patients who were approached to participate, declined participation and consented to participate (recruitment) [ Time Frame: 3 years ]
  • Proportion of patients who completed each visit within the trial (retention) [ Time Frame: 3 years ]
  • Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures) [ Time Frame: 3 years ]
  • Number of patients enrolled in the study compared to the number of patients who were able to complete study measures (tolerability with outcome measures) [ Time Frame: 3 years ]

Central Contacts and Locations

Central contacts

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

416-813-7353ann.yeh@sickkids.ca

Brenna Wong

416-813-7654brenna.wong@sickkids.ca

Locations

The Hospital for Sick Children

Recruiting

Toronto, Ontario, Canada, M5G 1X8

Contacts

Brenna Wong

416-813-7654brenna.wong@sickkids.ca

More Information

Sponsor

The Hospital for Sick Children

Last update posted

Sep 23, 2025

Last verified

Sep, 2025

Keywords

  • remyelination
  • youth
  • white matter
  • neural precursor cells
  • clinical trial
  • metformin

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by The Hospital for Sick Children on 2025-09-23. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.