Clinical trial NCT04121468: A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children With Multiple Sclerosis
Official title: A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis (MS)
Keywords: remyelination
youth
white matter
neural precursor cells
clinical trial
metformin
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Queen's University
name: Ontario Institute for Regenerative Medicine
name: Unity Health Toronto
name: Stem Cell Network
name: Multiple Sclerosis Society of Canada
First posted: 2019-10-10
Enrollment: 30
Sex: ALL
Minimum age (years): 10
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multiple baseline
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Number of patients with adverse events (safety and tolerability)
timeFrame: 3 years
measure: Number of patients who were approached to participate, declined participation and consented to participate (recruitment)
timeFrame: 3 years
measure: Proportion of patients who completed each visit within the trial (retention)
timeFrame: 3 years
measure: Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures)
timeFrame: 3 years
measure: Number of patients enrolled in the study compared to the number of patients who were able to complete study measures (tolerability with outcome measures)
timeFrame: 3 years
Secondary outcomes:
measure: Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness
timeFrame: 3 years
measure: Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness
timeFrame: 3 years
measure: Optical Coherence Tomography (OCT) - Optic Nerve Head Volume
timeFrame: 3 years
measure: Visual Evoked Potentials (VEP) - p100
timeFrame: 3 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: E. Ann Yeh, MA, MD, FRCPC, Dip ABPN
role: PRINCIPAL_INVESTIGATOR
References: