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

NCT ID: NCT04121468

Last Updated: 2025-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-24

Study Completion Date

2027-10-31

Brief Summary

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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

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Conditions

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Multiple Sclerosis (MS)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multiple baseline
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group A

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 Type OTHER

Metformin

Intervention Type DRUG

Each tablet contains 500mg of metformin hydrochloride

Placebo

Intervention Type OTHER

Each tablet contains no active drug ingredient

Group B

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 Type OTHER

Metformin

Intervention Type DRUG

Each tablet contains 500mg of metformin hydrochloride

Placebo

Intervention Type OTHER

Each tablet contains no active drug ingredient

Group C

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 Type OTHER

Metformin

Intervention Type DRUG

Each tablet contains 500mg of metformin hydrochloride

Placebo

Intervention Type OTHER

Each tablet contains no active drug ingredient

Interventions

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Metformin

Each tablet contains 500mg of metformin hydrochloride

Intervention Type DRUG

Placebo

Each tablet contains no active drug ingredient

Intervention Type OTHER

Other Intervention Names

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Glucophage

Eligibility Criteria

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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
Minimum Eligible Age

10 Years

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Queen's University

OTHER

Sponsor Role collaborator

Ontario Institute for Regenerative Medicine

UNKNOWN

Sponsor Role collaborator

Unity Health Toronto

OTHER

Sponsor Role collaborator

Stem Cell Network

OTHER

Sponsor Role collaborator

Multiple Sclerosis Society of Canada

OTHER

Sponsor Role collaborator

The Hospital for Sick Children

OTHER

Sponsor Role lead

Responsible Party

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E. Ann Yeh

Senior Associate Scientist, Division of Neuroscience and Mental Health, SickKids Research Institute

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

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The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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

Role: CONTACT

416-813-7353

Brenna Wong

Role: CONTACT

416-813-7654 ext. 415744

Facility Contacts

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Brenna Wong

Role: primary

416-813-7654 ext. 415744

Other Identifiers

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1000059119

Identifier Type: -

Identifier Source: org_study_id

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