A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children With Multiple Sclerosis
- Registration Number
- NCT04121468
- Lead Sponsor
- The Hospital for Sick Children
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 30
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B Metformin 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. Group B Placebo 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. Group C Metformin 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. Group C Placebo 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. Group A Metformin 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. Group A Placebo 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.
- Primary Outcome Measures
Name Time Method Proportion of patients who completed each visit within the trial (retention) 3 years Number of patients with adverse events (safety and tolerability) 3 years Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures) 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) 3 years Number of patients who were approached to participate, declined participation and consented to participate (recruitment) 3 years
- Secondary Outcome Measures
Name Time Method Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness 3 years Optical Coherence Tomography (OCT) - Optic Nerve Head Volume 3 years Visual Evoked Potentials (VEP) - p100 3 years Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness 3 years
Trial Locations
- Locations (2)
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada