We will be posting a series of summaries from our 2016 researcher meeting, highlighting some of the most interesting new developments and discoveries presented there. This update covers a session on clinical research and outcome measures. The goal of this session is to present the results of important studies that could influence clinical trial design or drug development. The session was moderated by Thomas Crawford, MD.

The session began with a talk by Holly Peay, PhD, (RTI International) on two topics. The first was about parental decision making about clinical trial participation. Because there are significant challenges associated with clinical trial design and recruitment in the context of SMA, it is important to understand the factors that contribute to the decision of parents to enroll their children. To that end, an online survey was conducted to learn from participants of both SMA and Duchenne/Becker muscular dystrophy trials.

Overall, participants were favorable towards trial participation. Some barriers to trial participation included: the possibility of receiving placebo instead of drug, the need for more information about trial risks, lack of potential benefits, and the need for more information about day-to-day requirements. Parents were more likely to enroll their children due to: confidence in the trial and researcher, access to trials and to the drug post-trial, and recommended trial participation from a physician. From the survey, the researchers concluded that families should have access to balanced educational materials and targeted clinical communications in order to facilitate informed trial decision making.

Dr. Peay finished her talk by presenting information about parental decision making in voluntary newborn screening. Information from parents was collected through an online survey. There was strong support for newborn screening with parental permission. Newborn screening could reduce time to diagnosis, improve management, inform reproductive risk, and provide the opportunity to enroll in trials. In order for parents to make an informed decision about voluntary screening, education and consent materials must meet high disclosure standards and help parents consider how screening aligns with their goals, values, and preferences.

Next Brett Bartels, MD, (University Medical Center Utrecht) addressed how susceptible those with SMA are to fatigue. 50% of SMA patients report fatigue during repetitive daily activities such as writing or drinking from a glass. This susceptibility to fatigue is often called “fatigability.” Because there are currently no validated clinical tests to access fatigability, a set of tests for both ambulatory (able to walk) and non-ambulatory patients was developed. The team is currently using those tests to try to determine possible causes of fatigability such as severity of disease, age, and neuromuscular junction function. Learning the cause of fatigability will aid in the development of therapies to combat it.

Linda Lowes, PhD, (Nationwide Children’s Hospital) discussed her findings on the best test to evaluate SMA type 1 infant motor function. For infants with SMA type 1, the ability to detect small changes in motor function is important, especially in the context of clinical trials. The researchers found that the ACTIVE-mini, which uses the Microsoft Kinect to track movement, was able to measure changes in movement ability of infants and children with SMA over time. Furthermore, the ease of administration and minimal stress the test places on the infant make the ACTIVE-mini a promising test for evaluating motor function in SMA infants.

To end the session, Steve Kolb, MD, PhD, (Ohio State University) presented results from the NeuroNEXT SMA infant biomarker study. This was a study to characterize natural history and biomarkers in infants with spinal muscular atrophy (SMA) and healthy infants in a control group. Infants with genetically confirmed SMA and healthy infants were enrolled prior to 6 months of age and followed serially for up to 24 months. The study was conducted at fifteen study sites of the NINDS NeuroNEXT Clinical Trial Network. Enrollment began November 2012 and ended September 2014 with 26 SMA infants and 27 healthy infants enrolled. Average age at enrollment visit was (mean±SD) 3.7±1.7 months for the SMA cohort and 3.3±2.0 months for the control cohort.

Birth weight and length, gender distribution, ethnicity and gestational ages were equivalent in the SMA and control cohorts. SMA infants demonstrate significant reductions in motor function (TIMPSI and CHOP-INTEND) and reduction in CMAP, an electrical study of muscle function, amplitudes at their first study visit. EIM, a non-invasive technique for the assessment of muscle health, is able to distinguish between SMA and healthy infants. The NeuroNEXT SMA Biomarker Study exceeded enrollment targets and had excellent retention of subjects. The SMA and control cohorts are well matched and provide natural history data in a multicenter context that may help to accelerate the development of therapies in the SMA infant population.

Pictured above: Dr. Tom Crawford speaks at the special session.