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

Multiple Sclerosis (MS) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04121468
• Other study ID #: 1000059119
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 24, 2020
• Est. completion date: December 2023

Study information

• Verified date: March 2022
• Source: The Hospital for Sick Children
• Contact: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN
• Phone: 416-813-7353
• Email: ann.yeh[@]sickkids.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis (MS)
• Sclerosis

Intervention

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

Other:
• Placebo
Each tablet contains no active drug ingredient

Locations

Country	Name	City	State
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (6)

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

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with adverse events (safety and tolerability)		3 years
Primary	Number of patients who were approached to participate, declined participation and consented to participate (recruitment)		3 years
Primary	Proportion of patients who completed each visit within the trial (retention)		3 years
Primary	Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures)		3 years
Primary	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	Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness		3 years
Secondary	Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness		3 years
Secondary	Optical Coherence Tomography (OCT) - Optic Nerve Head Volume		3 years
Secondary	Visual Evoked Potentials (VEP) - p100		3 years