Overview

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.

Eligibility

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
• Retinal Nerve Fiber Layer (RNFL) Thickness on baseline OCT ≥60 µm
• Stable immunomodulatory therapy - no switch or planned switch in > 6 months and no change in doses in 30 days prior to screening
• 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 (male)=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)
          -  Severe refractive error (± 6 diopters)
          -  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