A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children and Young Adults With Multiple Sclerosis

Treatment tested

• Metformin

Placebo or sham

• Placebo

Other measures (4)

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

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.