TY - JOUR
T1 - Clinical trials in REM sleep behavioural disorder
T2 - Challenges and opportunities
AU - Videnovic, Aleksandar
AU - Ju, Yo El S.
AU - Arnulf, Isabelle
AU - Cochen-De Cock, Valérie
AU - Cochen-De Cock, Valérie
AU - Högl, Birgit
AU - Kunz, Dieter
AU - Provini, Federica
AU - Provini, Federica
AU - Ratti, Pietro Luca
AU - Schiess, Mya C.
AU - Schenck, Carlos H.
AU - Schenck, Carlos H.
AU - Trenkwalder, Claudia
AU - Trenkwalder, Claudia
N1 - Funding Information:
1Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA 2Department of Neurology, washington University in Saint Louis, Saint Louis, Missouri, USA 3Assistance Publique Hôpitaux de Paris, Service des pathologies du Sommeil, Hôpital Pitié-Salpêtrière, Paris, France 4UMR S 1127, CNRS UMR 7225, iCM, Sorbonne Universités, UPMC University Paris, Paris, France 5Neurologie et sommeil, Clinique Beau Soleil, Montpellier, France 6Laboratoire Movement to Health (M2H), euroMov, Université Montpellier, Montpellier, France 7Department of Neurology, innsbruck Medical University, innsbruck, Austria 8Clinic for Sleep and Chronomedicine, Berlin, Germany 9iRCCS institute of Neurological Sciences of Bologna, University of Bologna, Bologna, italy 10Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, italy 11Neurocenter of Southern Switzerland, Lugano, Switzerland 12Department of Neurology, University of Texas Medical School at Houston, Houston, Texas, USA 13Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA 14Minnesota Regional Sleep Disorders Center, Minneapolis, Minnesota, USA 15Paracelsus elena Klinik, Kassel, Germany 16Department of Neurosurgery, University Medical Center, Göttingen, Germany Contributors Av: planning, conduct and reporting of the study; responsible for the overall content as guarantor. Y-eSJ: planning, conduct and reporting of the study. iA: planning, conduct and reporting of the study. vC-DC: planning, conduct and reporting of the study. BH: planning, conduct and reporting of the study. FP: planning, conduct and reporting of the study. P-LR: planning, conduct and reporting of the study. MS: planning, conduct and reporting of the study. CS: planning, conduct and reporting of the study. CT: planning, conduct and reporting of the study. funding This study was supported by these research grants from the National institutes of Health: K23NS089922, R21 NS108022, R34AG056639, UL1RR024992 Sub-Award KL2TR000450, UL1TR000448.
Publisher Copyright:
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - The rapid eye movement sleep behavioural disorder (RBD) population is an ideal study population for testing disease-modifying treatments for synucleinopathies, since RBD represents an early prodromal stage of synucleinopathy when neuropathology may be more responsive to treatment. While clonazepam and melatonin are most commonly used as symptomatic treatments for RBD, clinical trials of symptomatic treatments are also needed to identify evidence-based treatments. A comprehensive framework for both disease-modifying and symptomatic treatment trials in RBD is described, including potential treatments in the pipeline, cost-effective participant recruitment and selection, study design, outcomes and dissemination of results. For disease-modifying treatment clinical trials, the recommended primary outcome is phenoconversion to an overt synucleinopathy, and stratification features should be used to select a study population at high risk of phenoconversion, to enable more rapid clinical trials. For symptomatic treatment clinical trials, objective polysomnogram-based measurement of RBD-related movements and vocalisations should be the primary outcome measure, rather than subjective scales or diaries. Mobile technology to enable objective measurement of RBD episodes in the ambulatory setting, and advances in imaging, biofluid, tissue, and neurophysiological biomarkers of synucleinopathies, will enable more efficient clinical trials but are still in development. Increasing awareness of RBD among the general public and medical community coupled with timely diagnosis of these diseases will facilitate progress in the development of therapeutics for RBD and associated neurodegenerative disorders.
AB - The rapid eye movement sleep behavioural disorder (RBD) population is an ideal study population for testing disease-modifying treatments for synucleinopathies, since RBD represents an early prodromal stage of synucleinopathy when neuropathology may be more responsive to treatment. While clonazepam and melatonin are most commonly used as symptomatic treatments for RBD, clinical trials of symptomatic treatments are also needed to identify evidence-based treatments. A comprehensive framework for both disease-modifying and symptomatic treatment trials in RBD is described, including potential treatments in the pipeline, cost-effective participant recruitment and selection, study design, outcomes and dissemination of results. For disease-modifying treatment clinical trials, the recommended primary outcome is phenoconversion to an overt synucleinopathy, and stratification features should be used to select a study population at high risk of phenoconversion, to enable more rapid clinical trials. For symptomatic treatment clinical trials, objective polysomnogram-based measurement of RBD-related movements and vocalisations should be the primary outcome measure, rather than subjective scales or diaries. Mobile technology to enable objective measurement of RBD episodes in the ambulatory setting, and advances in imaging, biofluid, tissue, and neurophysiological biomarkers of synucleinopathies, will enable more efficient clinical trials but are still in development. Increasing awareness of RBD among the general public and medical community coupled with timely diagnosis of these diseases will facilitate progress in the development of therapeutics for RBD and associated neurodegenerative disorders.
KW - Lewy body dementia
KW - Parkinson's disease
KW - randomised trials
KW - sleep disorders
UR - http://www.scopus.com/inward/record.url?scp=85086749427&partnerID=8YFLogxK
U2 - 10.1136/jnnp-2020-322875
DO - 10.1136/jnnp-2020-322875
M3 - Review article
C2 - 32404379
AN - SCOPUS:85086749427
SN - 0022-3050
VL - 91
SP - 740
EP - 749
JO - Journal of Neurology Neurosurgery and Psychiatry
JF - Journal of Neurology Neurosurgery and Psychiatry
IS - 7
ER -