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

Primary Purpose

Multiple Sclerosis (MS)

Status

Recruiting

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Metformin

Placebo

About this trial

This is an interventional treatment trial for Multiple Sclerosis (MS) focused on measuring remyelination, youth, white matter, neural precursor cells, clinical trial, metformin

Eligibility Criteria

10 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

St. Michael's Hospital
The Hospital for Sick ChildrenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Arm Label

Group A

Group B

Group C

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of patients with adverse events (safety and tolerability)

Number of patients who were approached to participate, declined participation and consented to participate (recruitment)

Proportion of patients who completed each visit within the trial (retention)

Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures)

Number of patients enrolled in the study compared to the number of patients who were able to complete study measures (tolerability with outcome measures)

Secondary Outcome Measures

Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness

Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness

Optical Coherence Tomography (OCT) - Optic Nerve Head Volume

Visual Evoked Potentials (VEP) - p100

Full Information

NCT ID

NCT04121468

First Posted

October 2, 2019

Last Updated

March 15, 2022

Sponsor

The Hospital for Sick Children

Collaborators

Queen's University, Ontario Institute for Regenerative Medicine, Unity Health Toronto, Stem Cell Network, Multiple Sclerosis Society of Canada

1. Study Identification

Unique Protocol Identification Number

NCT04121468

Brief Title

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

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 24, 2020 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Hospital for Sick Children

Collaborators

Queen's University, Ontario Institute for Regenerative Medicine, Unity Health Toronto, Stem Cell Network, Multiple Sclerosis Society of Canada

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis (MS)

Keywords

remyelination, youth, white matter, neural precursor cells, clinical trial, metformin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Multiple baseline

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group A

Arm Type

Other

Arm Description

Arm Title

Group B

Arm Type

Other

Arm Description

Arm Title

Group C

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

Glucophage

Intervention Description

Each tablet contains 500mg of metformin hydrochloride

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Each tablet contains no active drug ingredient

Primary Outcome Measure Information:

Title

Number of patients with adverse events (safety and tolerability)

Time Frame

3 years

Title

Number of patients who were approached to participate, declined participation and consented to participate (recruitment)

Time Frame

3 years

Title

Proportion of patients who completed each visit within the trial (retention)

Time Frame

3 years

Title

Proportion of patients who completed each of the outcome measures at the appropriate time points (adherence with outcome measures)

Time Frame

3 years

Title

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

Secondary Outcome Measure Information:

Title

Optical Coherence Tomography (OCT) - Retinal Nerve Fiber Layer Thickness

Time Frame

3 years

Title

Optical Coherence Tomography (OCT) - Ganglion Cell Inner Plexiform Layer Thickness

Time Frame

3 years

Title

Optical Coherence Tomography (OCT) - Optic Nerve Head Volume

Time Frame

3 years

Title

Visual Evoked Potentials (VEP) - p100

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Maximum Age & Unit of Time

25 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

E. Ann Yeh, MA, MD, FRCPC, Dip ABPN

Phone

416-813-7353

ann.yeh@sickkids.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Shamashtika Thilagaratnam, BSc

Phone

416-813-7654

Ext

328190

shamashtika.thilagaratnam@sickkids.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

E. Ann Yeh, MA, MD, FRCPC, Dip ABPN

Organizational Affiliation

The Hospital for Sick Children

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Michael's Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5B 1W8

Country

Canada

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jiwon Oh, MD, PhD

First Name & Middle Initial & Last Name & Degree

Jiwon Oh, MD, PhD

Facility Name

The Hospital for Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X8

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shamashtika Thilagaratnam, BSc

Phone

4168137654

Ext

328190

shamashtika.thilagaratnam@sickkids.ca

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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