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

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

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.

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