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

March 15, 2022 updated by: E. Ann Yeh, The Hospital for Sick Children
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.

Study Overview

Status

Recruiting

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN
  • Phone Number: 416-813-7353
  • Email: ann.yeh@sickkids.ca

Study Contact Backup

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
      • Toronto, Ontario, Canada, M5B 1W8
        • Not yet recruiting
        • St. Michael's Hospital
        • Contact:
          • Jiwon Oh, MD, PhD
        • Principal Investigator:
          • Jiwon Oh, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.

Each tablet contains 500mg of metformin hydrochloride
Other Names:
  • Glucophage
Each tablet contains no active drug ingredient
Other: 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.

Each tablet contains 500mg of metformin hydrochloride
Other Names:
  • Glucophage
Each tablet contains no active drug ingredient
Other: 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.

Each tablet contains 500mg of metformin hydrochloride
Other Names:
  • Glucophage
Each tablet contains no active drug ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of patients with adverse events (safety and tolerability)
Time Frame: 3 years
3 years
Number of patients who were approached to participate, declined participation and consented to participate (recruitment)
Time Frame: 3 years
3 years
Proportion of patients who completed each visit within the trial (retention)
Time Frame: 3 years
3 years
Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures)
Time Frame: 3 years
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)
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness
Time Frame: 3 years
3 years
Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness
Time Frame: 3 years
3 years
Optical Coherence Tomography (OCT) - Optic Nerve Head Volume
Time Frame: 3 years
3 years
Visual Evoked Potentials (VEP) - p100
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN, The Hospital for Sick Children

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 24, 2020

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

October 2, 2019

First Submitted That Met QC Criteria

October 8, 2019

First Posted (Actual)

October 10, 2019

Study Record Updates

Last Update Posted (Actual)

March 16, 2022

Last Update Submitted That Met QC Criteria

March 15, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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