Multiple Sclerosis (MS)Phase 1/2NCT04121468
A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children and Young Adults With Multiple Sclerosis
A Phase 1/2 study testing Metformin in people with Multiple Sclerosis (MS), run by The Hospital for Sick Children at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 10 to 25 years
- Conditions the study is for
- Multiple Sclerosis (MS)
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 24 Feb 2020to Oct 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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, or Retinal Nerve Fiber Layer (RNFL) thickness on OCT of < 90 µm in at least one eye or an inter-eye difference in the RNFL of 10 µm or more
- Retinal Nerve Fiber Layer (RNFL) Thickness on baseline OCT ≥60 µm
- If on an MS disease-modifying therapy, no changes in the therapeutic agent or dosing in the 6 months prior to study initiation
- No significant renal or liver abnormalities
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- 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 (female)=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
Who cannot join
- A history of retinal pathology (major ophthalmologic disease / concomitant ophthalmologic disorders)
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Brenna Wong, 416-813-7654 ext. 415744, brenna.wong@sickkids.ca
About this study
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.
- Conditions
- Multiple Sclerosis (MS)
- Being tested
- Metformin, Placebo
- Keywords
- remyelination, youth, white matter, neural precursor cells, clinical trial, metformin
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
Each tablet contains 500mg of metformin hydrochloride
PlaceboOther
Each tablet contains no active drug ingredient
| Study group | Role | What they receive |
|---|---|---|
| Group A | Other | 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. Receives: Drug: Metformin; Other: Placebo |
| Group B | Other | 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. Receives: Drug: Metformin; Other: Placebo |
| Group C | Other | 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. Receives: Drug: Metformin; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events (safety and tolerability)
Measured: 3 years
Number of patients who were approached to participate, declined participation and consented to participate (recruitment)
Measured: 3 years
Proportion of patients who completed each visit within the trial (retention)
Measured: 3 years
Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures)
Measured: 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)
Measured: 3 years
Secondary outcomes (4)
Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness
Measured: 3 years
Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness
Measured: 3 years
Optical Coherence Tomography (OCT) - Optic Nerve Head Volume
Measured: 3 years
Visual Evoked Potentials (VEP) - p100
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2019
- Study start24 Feb 2020
- Primary completionMar 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis (MS)Studies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multiple baseline
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Queen's University, Ontario Institute for Regenerative Medicine, Unity Health Toronto, Stem Cell Network, Multiple Sclerosis Society of Canada
- Responsible party
- Principal investigator, E. Ann Yeh, The Hospital for Sick Children
- Investigators
- E. Ann Yeh, MA, MD, FRCPC, Dip ABPN, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04121468
- Sponsor's protocol ID
- 1000059119
- Status last verified
- Sep 2025
- First submitted
- 2 Oct 2019
- Last updated
- 23 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Double Blind Study of Metformin Acting on Endogenous Neural Progenitor Cells in Children and Young Adults With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT04121468
- Acronym / sponsor ID
- 1000059119
- Conditions
- Multiple Sclerosis (MS)
- Keywords
- remyelination, youth, white matter, neural precursor cells, clinical trial, metformin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Queen's University, Ontario Institute for Regenerative Medicine, Unity Health Toronto, Stem Cell Network, Multiple Sclerosis Society of Canada
- Study start
- 24 Feb 2020 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 10 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Multiple baseline
| Arm | Type | Receives |
|---|---|---|
| Group A | Other | Drug: Metformin, Other: PlaceboPlacebo 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. |
| Group B | Other | Drug: Metformin, Other: PlaceboPlacebo 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. |
| Group C | Other | Drug: Metformin, Other: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 10 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- 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, or Retinal Nerve Fiber Layer (RNFL) thickness on OCT of < 90 µm in at least one eye or an inter-eye difference in the RNFL of 10 µm or more
- Retinal Nerve Fiber Layer (RNFL) Thickness on baseline OCT ≥60 µm
- If on an MS disease-modifying therapy, no changes in the therapeutic agent or dosing in the 6 months prior to study initiation
Key exclusion criteria (10 listed)
- A history of retinal pathology (major ophthalmologic disease / concomitant ophthalmologic disorders)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: GlucophageEach tablet contains 500mg of metformin hydrochloride | Drug | Group A, Group B, Group C |
| PlaceboEach tablet contains no active drug ingredient | Other | Group A, Group B, Group C |
Primary outcome
Number of patients with adverse events (safety and tolerability)
Time frame: 3 years
Number of patients who were approached to participate, declined participation and consented to participate (recruitment)
Time frame: 3 years
Proportion of patients who completed each visit within the trial (retention)
Time frame: 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
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
4 secondary outcomes
Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness
Time frame: 3 years
Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness
Time frame: 3 years
Optical Coherence Tomography (OCT) - Optic Nerve Head Volume
Time frame: 3 years
Visual Evoked Potentials (VEP) - p100
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
E. Ann Yeh, MA, MD, FRCPC, Dip ABPN principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Metformin in people with Multiple Sclerosis (MS), run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact E. Ann Yeh, MA, MD, FRCPC, Dip ABPN (416-813-7353, ann.yeh@sickkids.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events (safety and tolerability) (time frame: 3 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2025.