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

NCT04121468 | Recruiting Phase 1 DMC

• 1 other identifier: 1000059119
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis (MS)

Keywords

remyelination; youth; white matter; neural precursor cells; clinical trial; metformin

Outcome Measures

Primary Outcomes (5)

• 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

• 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

Secondary Outcomes (4)

• Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness

  3 years

• 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

Study Arms (3)

Group A

OTHER

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.

Drug: Metformin; Other: Placebo

Group B

OTHER

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.

Drug: Metformin; Other: Placebo

Group C

OTHER

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.

Drug: Metformin; Other: Placebo

Interventions

Metformin DRUG

Each tablet contains 500mg of metformin hydrochloride

Also known as: Glucophage

Group A; Group B; Group C

Placebo OTHER

Each tablet contains no active drug ingredient

Group A; Group B; Group C

Eligibility Criteria

• Age: 10 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Queen's University: collaborator
• Ontario Institute for Regenerative Medicine: collaborator
• Unity Health Toronto: collaborator
• Stem Cell Network: collaborator
• Multiple Sclerosis Society of Canada: collaborator

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Metformin

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• E. Ann Yeh, MA, MD, FRCPC, Dip ABPN

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Central Study Contacts

E. Ann Yeh, MA, MD, FRCPC, Dip ABPN

CONTACT

416-813-7353; ann.yeh@sickkids.ca

Brenna Wong

CONTACT

416-813-7654; brenna.wong@sickkids.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Associate Scientist, Division of Neuroscience and Mental Health, SickKids Research Institute

Model Details: Multiple baseline

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 10, 2019
• Study Start: February 24, 2020
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)