Studies to Test Diabetes Treatment, Metformin, on Fragile X Patients Now Enrolling in US and Canada

An upcoming clinical trial will examine if a diabetes medicine has behavioral and cognitive effects on children and young adults with fragile X syndrome.

Treating the symptoms of fragile X usually relies on non-pharmacological interventions, like speech and occupational therapy. As of now, no medications have proven effective in treating key symptoms of this disease.

“Working with the brain is very challenging,” Francois Bolduc, MD, PhD, a professor at the University of Alberta and a leading researcher for the new trials, said in a press release, “but we’ve found a drug that could have a huge impact on treating individuals with FXS [fragile X].”

That medicine is metformin, which is typically used to help control blood sugar levels in people with diabetes. But metformin affects the body in a number of ways; in animal models, it was shown to improve communication between brain cells, which is commonly impaired in fragile X.

There’s also some evidence for metformin being effective in fragile X patients, but no clinical trial has tested the medicine for this purpose.

“We aren’t developing a cure,” Bolduc said. “Our goal is to develop a treatment that helps improve quality of life — like daily functioning, learning and anxiety — because symptoms like these impact not only the individual, but the family as a whole.”

In line with this way of thinking, the trial will include assessments of quality of life and economic strain, in addition to measuring cognition and behavior.

“If a child’s symptoms are better managed, they have the potential to have more independence long-term, but we also want to know if their parents are able to be more independent,” Buldoc said, adding, “[t]he economic impact for families with a child with FXS is huge: about $30,000 to $40,000 a year.”

The trial  is being conducted at the University of Alberta and Montreal’s Sainte-Justine University Hospital Center (NCT03862950), and at the University of California Davis MIND Institute (NCT03479476). All sites are or will soon recruit fragile X patients between the ages of 6 and 25. Interested parties can click here for information on the Canadian trial sites, or here to learn more about enrolling in the UC Davis study, whose principal investigator is Randi Hagerman, MD.

Participants will be randomized to either metformin or placebo, and will attend three visits to their study site over a four-month period for testing. The primary objectives are to assess the safety, tolerability, and efficacy of metformin in treating language deficits, behavior problems, and obesity or excessive appetite.

Buldoc and colleagues will also collect blood and urine samples and — using cells obtained from these samples — develop stem cells that can be converted into brain cells, allowing researchers to study how these patients respond to metformin treatment at the cellular level.

“What we’re doing is completely novel,” Bolduc said. “We’re looking to suss out any markers in the body that can predict whether or not an individual with FXS will benefit from metformin treatment.”