Rethinking clinical trials in restless legs syndrome: A roadmap
Recommended Citation
Garcia-Borreguero D, Black J, Earley CJ, Fulda S, Högl B, Manconi M, Ondo W, Roth T, Trenkwalder C, and Winkelman JW. Rethinking clinical trials in restless legs syndrome: A roadmap. Sleep Med Rev 2024; 77:101978.
Document Type
Article
Publication Date
10-1-2024
Publication Title
Sleep medicine reviews
Abstract
The number of large clinical trials of restless legs syndrome (RLS) have decreased in recent years, this coincides with reduced interest in developing and testing novel pharmaceuticals. Therefore, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force of global experts to examine the causes of these trends and make recommendations to facilitate new clinical trials. In our article, we delve into potential complications linked to the diagnostic definition of RLS, identify subpopulations necessitating more attention, and highlight issues pertaining to endpoints and study frameworks. In particular, we recommend developing alternative scoring methods for more accurate RLS diagnosis, thereby improving clinical trial specificity. Furthermore, enhancing the precision of endpoints will increase study effect sizes and mitigate study costs. Suggestions to achieve this include developing online, real-time sleep diaries with high-frequency sampling of nightly sleep latency and the use of PLMs as surrogate markers. Furthermore, to reduce the placebo response, strategies should be adopted that include placebo run-in periods. As RLS is frequently a chronic condition, priority should be given to long-term studies, using a randomized, placebo-controlled, withdrawal design. Lastly, new populations should be investigated to develop targeted treatments such as mild RLS, pregnancy, hemodialysis, or iron-deficient anemia.
Medical Subject Headings
Restless Legs Syndrome; Humans; Clinical Trials as Topic; Research Design
PubMed ID
39102777
Volume
77
First Page
101978
Last Page
101978
