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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04121468
Recruitment Status : Recruiting
First Posted : October 10, 2019
Last Update Posted : March 16, 2022
Sponsor:
Collaborators:
Queen's University
Ontario Institute for Regenerative Medicine
Unity Health Toronto
Stem Cell Network
Multiple Sclerosis Society of Canada
Information provided by (Responsible Party):
E. Ann Yeh, The Hospital for Sick Children

Study Description
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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
Multiple Sclerosis (MS) Drug: Metformin Other: Placebo Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multiple 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 : February 24, 2020
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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 Name: Glucophage

Other: Placebo
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.

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

Other: Placebo
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.

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

Other: Placebo
Each tablet contains no active drug ingredient


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

Secondary Outcome Measures :
  1. Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness [ Time Frame: 3 years ]
  2. Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness [ Time Frame: 3 years ]
  3. Optical Coherence Tomography (OCT) - Optic Nerve Head Volume [ Time Frame: 3 years ]
  4. Visual Evoked Potentials (VEP) - p100 [ Time Frame: 3 years ]

Eligibility Criteria
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Ages Eligible for Study:   10 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04121468


Contacts
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Contact: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN 416-813-7353 ann.yeh@sickkids.ca
Contact: Shamashtika Thilagaratnam, BSc 416-813-7654 ext 328190 shamashtika.thilagaratnam@sickkids.ca

Locations
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Canada, Ontario
St. Michael's Hospital Not yet recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Jiwon Oh, MD, PhD         
Principal Investigator: Jiwon Oh, MD, PhD         
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Shamashtika Thilagaratnam, BSc    4168137654 ext 328190    shamashtika.thilagaratnam@sickkids.ca   
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
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Principal Investigator: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN The Hospital for Sick Children
More Information
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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: October 10, 2019    Key Record Dates
Last Update Posted: March 16, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by E. Ann Yeh, The Hospital for Sick Children:
remyelination
youth
white matter
 neural precursor cells
clinical trial
metformin
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
 Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs