- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04121468
A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children With Multiple Sclerosis
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN
- Phone Number: 416-813-7353
- Email: ann.yeh@sickkids.ca
Study Contact Backup
- Name: Shamashtika Thilagaratnam, BSc
- Phone Number: 328190 416-813-7654
- Email: shamashtika.thilagaratnam@sickkids.ca
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 1X8
- Recruiting
- The Hospital for Sick Children
-
Contact:
- Shamashtika Thilagaratnam, BSc
- Phone Number: 328190 4168137654
- Email: shamashtika.thilagaratnam@sickkids.ca
-
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
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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:
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:
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:
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
Sponsor
Collaborators
Investigators
- Principal Investigator: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN, The Hospital for Sick Children
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1000059119
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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