Poster Abstract #13: Interactive Voice Response Diary and Objective Myotonia Measurement as Endpoints for Clinical Trials in Nondystrophic Interactive Voice Response Diary and Objective Myotonia Measurement as Endpoints for Clinical Trials in Nondystrophic Myotonia

Abstract

Background Nondystrophic myotonia (NDM) is a heterogeneous group of neuromuscular disorders caused by mutations in skeletal muscle sodium and chloride channels. There are no established treatments for myotonia, despite the availability of agents that deserve careful study. An outcome measure of myotonia is important for clinical trials. Methods 45 subjects were enrolled from six academic centers across the United States, England, and Canada. Patients were categorized as myotonia congenita (MC), paramyotonia congenita (PMC), and other myotonic disorders (OMD) Three possible myotonia (symptoms/signs) measures were assessed: relaxation time after maximum voluntary isometric contraction of the finger flexors (QMA); myotonic discharges on needle EMG; an Interactive Voice Response Diary (IVR), for which participants called in once a week for up to 8 weeks to rank symptom severity on a scale of 1 to 9 (stiffness, pain, weakness, fatigue) and frequency (1–7 days). Results Initial clinical diagnosis was 20 MC; 16 PMC; 9 OMD. Myotonic discharge potentials were seen in all subjects with no difference in their degree and location among the subtypes. Of 33 participants for whom QMA test results were available, 15 showed a delay in relaxation; however, for subjects with e 2's hand grip opening on clinical exam, 14/16 showed a delay in relaxation on QMA. From IVR data, frequency of symptoms for the total population was stiffness 91%, pain 60%, weakness 56%, and fatigue 65%. Average severity for each symptom was stiffness, 4.1; pain, 4.0; weakness, 4.2; and fatigue, 4.2. Standard deviation of reported symptom severity within subject was stiffness, 1.2; pain, 1.1; weakness, 1.3; and tiredness, 0.9. For participants reporting symptoms for a given week, the average number of days they experienced symptoms was stiffness, 5.2; pain, 5.2; weakness, 4.4; and fatigue, 4.5. Conclusions The IVR data showed consistency in patient self-rated clinical symptoms related to myotonia, which makes this a potentially useful endpoint for future clinical trials. Quantitive myotonia measure is a less sensitive outcome measure, because only minority patients showed abnormal results. This project is supported by NIH grant 5U54RRO19482.