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

Sponsor
The Hospital for Sick Children (Other)
Overall Status
Recruiting
CT.gov ID
NCT04121468
Collaborator
Queen's University (Other), Ontario Institute for Regenerative Medicine (Other), Unity Health Toronto (Other), Stem Cell Network (Other), Multiple Sclerosis Society of Canada (Other)
30
Enrollment
2
Locations
3
Arms
45.2
Anticipated Duration (Months)
15
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Multiple baselineMultiple baseline
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children With Multiple Sclerosis
Actual Study Start Date :
Feb 24, 2020
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

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.

Drug: Metformin
Each tablet contains 500mg of metformin hydrochloride
Other Names:
  • Glucophage

    • Other: Placebo
    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.

    Drug: Metformin
    Each tablet contains 500mg of metformin hydrochloride
    Other Names:
  • Glucophage

    • Other: Placebo
    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.

    Drug: Metformin
    Each tablet contains 500mg of metformin hydrochloride
    Other Names:
  • Glucophage

    • Other: Placebo
    Each tablet contains no active drug ingredient

    Outcome Measures

    Primary Outcome Measures

    1. Number of patients with adverse events (safety and tolerability) [3 years]

    2. Number of patients who were approached to participate, declined participation and consented to participate (recruitment) [3 years]

    3. Proportion of patients who completed each visit within the trial (retention) [3 years]

    4. Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures) [3 years]

    5. 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 Outcome Measures

    1. Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness [3 years]

    2. Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness [3 years]

    3. Optical Coherence Tomography (OCT) - Optic Nerve Head Volume [3 years]

    4. Visual Evoked Potentials (VEP) - p100 [3 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    10 Years to 25 Years
    Sexes Eligible for Study:
    All
    Accepts 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

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 St. Michael's Hospital Toronto Ontario Canada M5B 1W8
    2 The Hospital for Sick Children Toronto Ontario Canada M5G 1X8

    Sponsors and Collaborators

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

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    E. Ann Yeh, Senior Associate Scientist, Division of Neuroscience and Mental Health, SickKids Research Institute, The Hospital for Sick Children
    ClinicalTrials.gov Identifier:
    NCT04121468
    Other Study ID Numbers:
    • 1000059119
    First Posted:
    Oct 10, 2019
    Last Update Posted:
    Mar 16, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by E. Ann Yeh, Senior Associate Scientist, Division of Neuroscience and Mental Health, SickKids Research Institute, The Hospital for Sick Children
    remyelination
    youth
    white matter
    neural precursor cells
    clinical trial
    metformin
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Sclerosis
    Metformin

    Study Results

    No Results Posted as of Mar 16, 2022