Rethinking clinical trials in restless legs syndrome: A roadmap

IF 11.2 1区 医学 Q1 CLINICAL NEUROLOGY
Diego Garcia-Borreguero , Jed Black , Christopher J. Earley , Stephany Fulda , Birgit Högl , Mauro Manconi , William Ondo , Thomas Roth , Claudia Trenkwalder , John W. Winkelman , on behalf of the International Restless Legs Syndrome Study Group (IRLSSG)
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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.

重新思考不宁腿综合征的临床试验:路线图
近年来,针对不安腿综合征(RLS)的大型临床试验数量有所减少,这与开发和测试新型药物的兴趣降低不谋而合。因此,国际不安腿综合征研究小组(IRLSSG)成立了一个由全球专家组成的特别工作组,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,我们建议开发其他评分方法,以更准确地诊断 RLS,从而提高临床试验的特异性。此外,提高终点的精确度将增加研究的效应大小并降低研究成本。为此提出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,以及使用 PLM 作为替代标记物。此外,为减少安慰剂反应,应采取包括安慰剂运行期的策略。由于 RLS 通常是一种慢性疾病,因此应优先考虑采用随机、安慰剂对照、停药设计的长期研究。最后,应研究新的人群以开发有针对性的治疗方法,如轻度 RLS、妊娠、血液透析或缺铁性贫血。
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来源期刊
Sleep Medicine Reviews
Sleep Medicine Reviews 医学-临床神经学
CiteScore
20.10
自引率
3.80%
发文量
107
期刊介绍: Sleep Medicine Reviews offers global coverage of sleep disorders, exploring their origins, diagnosis, treatment, and implications for related conditions at both individual and public health levels. Articles comprehensively review clinical information from peer-reviewed journals across various disciplines in sleep medicine, encompassing pulmonology, psychiatry, psychology, physiology, otolaryngology, pediatrics, geriatrics, cardiology, dentistry, nursing, neurology, and general medicine. The journal features narrative reviews, systematic reviews, and editorials addressing areas of controversy, debate, and future research within the field.
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