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

• Status: Recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Hospital for Sick Children
• Collaborators: Multiple Sclerosis Society of Canada; Ontario Institute for Regenerative Medicine; Queen's University; Stem Cell Network; Unity Health Toronto
• Treatments: Metformin

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

• 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