Sleep Research Institute, Madrid, Spain.
Stanford University Center for Sleep Sciences and Medicine, Palo Alto, CA, USA; Jazz Pharmaceuticals, Palo Alto, CA, USA.
Sleep Med Rev. 2024 Oct;77:101978. doi: 10.1016/j.smrv.2024.101978. Epub 2024 Jul 18.
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.
近年来，关于不宁腿综合征（RLS）的大型临床试验数量有所减少，这与人们对开发和测试新型药物的兴趣降低有关。因此，国际不宁腿综合征研究组（IRLSSG）成立了一个由全球专家组成的工作组，研究这些趋势的原因，并提出建议，以促进新的临床试验。在我们的文章中，我们深入探讨了与 RLS 诊断定义相关的潜在并发症，确定了需要更多关注的亚人群，并强调了与终点和研究框架相关的问题。特别是，我们建议开发替代评分方法，以更准确地诊断 RLS，从而提高临床试验的特异性。此外，提高终点的精确性将增加研究的效果大小，并降低研究成本。实现这一目标的建议包括开发在线、实时睡眠日记，对夜间睡眠潜伏期进行高频采样，并使用周期性肢体运动（PLMs）作为替代标志物。此外，为了减少安慰剂反应，应采取包括安慰剂导入期在内的策略。由于 RLS 通常是一种慢性疾病，应优先考虑使用随机、安慰剂对照、撤药设计的长期研究。最后，应研究新的人群，以开发针对轻度 RLS、妊娠、血液透析或缺铁性贫血等疾病的靶向治疗方法。
