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

• Register: ClinicalTrials.gov
• Last refreshed on: 28 March 2022
• Main ID: NCT04121468
• Date of registration: 02/10/2019
• Prospective Registration: Yes
• Primary sponsor: The Hospital for Sick Children
• Public title: A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children With Multiple Sclerosis
• Scientific title: A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children With Multiple Sclerosis
• Date of first enrolment: February 24, 2020
• Target sample size: 30
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT04121468
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

Canada

Contacts

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

• Name: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN

Key inclusion & exclusion 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



Age minimum: 10 Years
Age maximum: 25 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis (MS)

Intervention(s)

Drug: Metformin

Other: Placebo

Primary Outcome(s)

Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures) [Time Frame: 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]

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

Number of patients with adverse events (safety and tolerability) [Time Frame: 3 years]

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

Secondary Outcome(s)

Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness [Time Frame: 3 years]

Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness [Time Frame: 3 years]

Visual Evoked Potentials (VEP) - p100 [Time Frame: 3 years]

Optical Coherence Tomography (OCT) - Optic Nerve Head Volume [Time Frame: 3 years]

Secondary ID(s)

1000059119

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Queen's University

Multiple Sclerosis Society of Canada

Ontario Institute for Regenerative Medicine

Unity Health Toronto

Stem Cell Network