Reassessing Clinical Trials Outcome Measures for Fragile X Syndrome Treatments

A recent review of 22 clinical trials testing new treatments for the genetic disease known as fragile X syndrome (FXS), has found that the use of more reliable outcome measures may be necessary in order to show treatment efficacy. The analysis was conducted by researchers across a number of research institutions in the US, with results of the study being published in the Journal of Neurodevelopmental Disorders.

“In an attempt to keep up with recent major discoveries in animal models of fragile X syndrome, and other developments, clinical studies in humans have unfolded on a fast track along an uncharted path, and several have unfortunately failed,” said first author Dr. Dejan Budimirovic, assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. He is also the medical co-director of the Fragile X Clinic at Kennedy Krieger Institute.

FXS is the most common cause of intellectual disability caused by an inherited mutation. Symptoms of FXS are similar to those observed in individuals with autism spectrum disorder (ASD), including attention deficit, hypersensitivity to sensory inputs and delayed speech.

Animal models of FXS have advanced substantially in recent years, providing researchers with better tools with which to test new FXS treatments. In addition to drug interventions, occupational, behavioral and speech therapy are often necessary when treating a patient with FXS.

According to Budimirovic, while previous clinical trial failures have helped identify new outcome measures to assess the efficacy of drugs for FXS, they have yet to be applied to all clinical trial designs for the genetic disorder. The goal of their recent publication was to update recommendations for FXS clinical trials from those previously published in 2013.

In their analysis, the researchers identified three outcome measures – cognition, behavior/emotion and medical/physical – that could help clinical trials investigators accurately assess new treatments. IQ tests, measurement of disruptive behaviors and biomarkers are all respective examples of the three outcome measures identified by Budimirovic and his colleagues.

The study authors also classified current outcome measures based on whether they would be more appropriate for use in short-term or longer-term clinical trials. They found that different measures may be better at detecting changes in FXS symptoms at different time points.

“While the present report suggests that optimal outcome measures for FXS are not yet fully developed, the recent failures of clinical trials in the FXS treatment field represent an opportunity to implement novel study designs and methodologies,” said Budimirovic.