Multiple Sclerosis (MS)
Conditions
Keywords
remyelination, youth, white matter, neural precursor cells, clinical trial, metformin
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.
Interventions
DRUGMetformin
Each tablet contains 500mg of metformin hydrochloride
OTHERPlacebo
Each tablet contains no active drug ingredient
Sponsors
Queen's University
Ontario Institute for Regenerative Medicine
Unity Health Toronto
Stem Cell Network
Multiple Sclerosis Society of Canada
The Hospital for Sick Children
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Multiple baseline
Eligibility
Sex/Gender
ALL
Age
10 Years to 25 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 with adverse events (safety and tolerability) | 3 years |
| Number of patients who were approached to participate, declined participation and consented to participate (recruitment) | 3 years |
| Proportion of patients who completed each visit within the trial (retention) | 3 years |
| Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures) | 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform 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) - Retinal Nerve Fiber Layer Thickness | 3 years |
Countries
Canada
Contacts
Primary ContactE. Ann Yeh, MA, MD, FRCPC, Dip ABPN
Backup ContactBrenna Wong
Outcome results
None listed