A Phase I double-blind study of metformin acting on endogenous neural progenitor cells in children with multiple sclerosis (MetF MS)


Study Title: A Phase I double-blind study of metformin acting on endogenous neural progenitor cells in children with multiple sclerosis (MetF MS)
Rationale: The research is being done to see if we can repair damaged myelin in youth and young adults with MS using a drug called metformin. Previous research has shown that metformin helps repair myelin in mice and may associate with decreased relapses in adults with MS and metabolic syndromes.
Study Description: Damage to white matter in the brain occurs in multiple sclerosis, and results in sensory, motor, and cognitive problems. Moreover, the economic burden of MS is significant. Multiple disease modifying therapies are available, including therapies that provide good control of inflammatory disease activity, but do not reverse the progressive nature of the disease. Costs of disease modifying therapies are high and costs of absenteeism due to MS and lost productivity amount to over 1/3 of the costs of MS. Importantly, the current standard of care includes only therapies that target inflammatory factors related to the disease: approaching the disease from a reparative perspective may have additional benefits.

Currently, while there is much research focused on repair and re-myelination, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In the proposed research, we hope to change this situation by enhancing the creation of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the creation of oligodendrocytes from neural precursors and that, following pediatric white matter injury, this promotes structural and functional recovery.

The use of metformin represents a highly innovative strategy to treat youth with MS. Finding a low-cost strategy may be of great benefit both to society and individuals with MS. This early phase trial will produce essential preliminary evidence for safety and tolerability of this approach.

In this study, participants will take metformin for either 3, 6, or 9 months depending on which group they are randomly assigned to. Participation will be for a total of 12 months and will require 5 visits to SickKids.

Positive results in our clinical trial will lead to a dramatic shift in how we treat youth with multiple sclerosis, and will pave the way for future additional clinical trials in children and adults with multiple sclerosis.
Recruitment Dates: 2021-01-01 to 2023-06-30
Who can participate: If you have been diagnosed with MS and are between the ages of 10 and 25 you may be eligible to participate.
Location of Trial: The Hospital for Sick Children
Contact Information: Dr. E. Ann Yeh