DREAMER - IsolateD REM Sleep Without Atonia as a Risk Factor for REM Sleep Behavior disordER

REM Sleep Behavior Disorder Clinical Trial

— DREAMER  

Official title:

DREAMER - IsolateD REM Sleep Without Atonia as a Risk Factor for REM Sleep Behavior disordER: Constitution of a Cohort for a Long-term Prospective Follow-up Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06140511
• Other study ID #: PNRR MR1 2022-12375694
• Secondary ID: PNRR MR1 2022-12
• Status: Not yet recruiting
• Start date: November 20, 2023
• Est. completion date: May 19, 2025

Study information

• Verified date: November 2023
• Source: Oasi Research Institute-IRCCS
• Contact: Lorenzo Mercadante, PhD
• Phone: +39 0935 936913
• Email: lmercadante[@]oasi.en.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims at the constitution of a large cohort of adult subjects without Rapid eye movement (REM) sleep behavior disorder (RBD), among whom subjects with isolated REM sleep without atonia (RSWA) will be identified; their long-term follow-up, compared to subjects without RSWA, will be useful in the next years to understand if this condition represents a risk factor for the future development of RBD, a condition in which the development of a neurodegenerative disorder (especially synucleinopathy) is highly probable. This will allow to obtain a wide time window for the establishment of prevention and neuroprotection in these subjects, with the goal to avoid or delay the development of the RBD>synucleinopathy sequence. All Units will recruit a large number of subjects without RBD undergoing a polysomnography (PSG) recording, with a shared protocol, and the data collected will be stored on a web-based common database. Subjects showing RSWA in their PSG will be identified and used as a prospective study group, which will start at the end of the recruitment of this project.

Description:

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. RBD-related dream enactment ranges in severity from benign hand gestures to violent thrashing, punching, and kicking. In spontaneously occurring cases, RBD is a prodromal syndrome of alpha-synuclein neurodegeneration. Thus, the vast majority of RBD patients will eventually demonstrate signs and symptoms of Parkinson disease (PD) or a related disorder (e.g., multiple system atrophy or dementia with Lewy bodies), often after a prolonged interval. REM sleep without atonia (RSWA) is the hallmark of RBD and a required criterion of its diagnosis, in agreement with the International Classification of Sleep Disorders-3rd revision; however, RSWA has been reported also in subjects without RBD, as an 'incidental' finding or as an effect of antidepressants. There is preliminary observational evidence that this "isolated" RSWA might indicate an increased risk for the future development of RBD, and its occurrence with antidepressants has been interpreted as a possible indication of an acceleration of a possible underlying neurodegeneration. The scientific community is actively seeking for effective neuroprotective agents, and the very early identification of subjects at risk, years or even decades before the occurrence of a clear neurodegeneration is crucially important. The cohort constituted with this study will be able to provide extremely useful answers to this problem.

With the exception of Unit 1, which will be in charge of the implementation of the web-based electronic Clinical Report Form for the storage of data collected by all Units, the clinical work-up of all Units will be harmonized during the first 6 months of the project in order to collect, for all subjects recruited, after obtaining their informed consent, a common core of clinical and instrumental features. Unit 1 will also be in charge of the Ethics Committee procedure for the approval of the protocol, which will be accomplished during the first 3 months of activity. Particular attention will be paid to the privacy and data protection aspects of the project by involving the experts with the appropriate competences available for the activities of Unit 1 at the Oasi Research Institute (Data Protection Officer and information technology expert, in particular). Beside the definition of the inclusion/exclusion criteria and of the common core of data to collect, the recruitment of subjects will be carried-out in a period of at least 18 months by all Units, which are equipped with all necessary tools for the recording, scoring and storage of polysomnography (PSG) exams. PSG exams will be used for the identification of subjects with RSWA by means of the computation of the REM atonia index (RAI). In addition to the PSG recording, which will be performed in all subjects recruited, and in agreement with previous preliminary data produced by our groups on the possible detection of early subtle changes by means of other neurophysiological parameters , Unit 1 will also perform a transcranial magnetic stimulation (TMS) study for the evaluation of the cortical excitability of subjects found having RSWA and in an adequate group of subjects without RSWA. Similarly, Unit 2 will perform a complete Vestibular Evoked Myogenic Potentials (VEMPs) study of subjects found having RSWA and in an adequate group of subjects without RSWA, whereas Units 3 and 4 will ensure the recording of the Brainstem Auditory Evoked Potentials (BAEPs), which both evaluate the brainstem functioning. Additional instrumental exams, such as brain imaging (magnetic resonance imaging/computerized tomography scan), dopamine transporter (DAT) scan, etc., will be performed on the basis of the clinical needs of the subjects, as a part of their clinical diagnostic work-up. Finally, whenever possible and especially for subjects with RSWA, blood samples will be adequately stored for a final proteomic and metabolomic analysis in order to establish if omics signatures are expressed in them similar to those that we have already found in RBD patients .

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 600
• Est. completion date: May 19, 2025
• Est. primary completion date: May 19, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• age =18 years

• sharing bedroom with a partner or roommate

• absence of a severe health, neurological, or cognitive problem that would impair the comprehension of the study tasks

• sleep recording without important artifact in the chin electromyographic signals, and presence of at least 5 min of REM sleep.

Exclusion Criteria:

• previous diagnosis of RBD,

Related Conditions & MeSH terms

• Mental Disorders
• REM Sleep Behavior Disorder

Intervention

Diagnostic Test:
• Polysomnography
Polysomnography for the assessment of the presence of REM sleep without atonia (RSWA). All Units will recruit subjects to be included in the cohort and this will ensure the inclusion of a sufficiently large sample of subjects without and, especially, with RSWA. From a previous study [Ferri et al. Sleep 2018:zsy187] that we carried out on a similar group of subjects, we know that we can expect to find RSWA in approximately 14% of individuals.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Oasi Research Institute-IRCCS	IRCCS San Raffaele, IRCCS- Institute of Neurological Sciences, Bologna, Italy, University of Cagliari, Cagliari, Italy

References & Publications (19)

Dijkstra F, Viaene M, Crosiers D, De Volder I, Cras P. Frequency and characteristic features of REM sleep without atonia. Clin Neurophysiol. 2019 Oct;130(10):1825-1832. doi: 10.1016/j.clinph.2019.07.018. Epub 2019 Jul 27. — View Citation

Dong X, Mondello S, Kobeissy F, Talih F, Ferri R, Mechref Y. LC-MS/MS glycomics of idiopathic rapid eye movement sleep behavior disorder. Electrophoresis. 2018 Dec;39(24):3096-3103. doi: 10.1002/elps.201800316. Epub 2018 Sep 12. — View Citation

Ferri R, Arico D, Cosentino FII, Lanuzza B, Chiaro G, Manconi M. REM sleep without atonia with REM sleep-related motor events: broadening the spectrum of REM sleep behavior disorder. Sleep. 2018 Dec 1;41(12). doi: 10.1093/sleep/zsy187. — View Citation

Ferri R, Bruni O, Fulda S, Zucconi M, Plazzi G. A quantitative analysis of the submentalis muscle electromyographic amplitude during rapid eye movement sleep across the lifespan. J Sleep Res. 2012 Jun;21(3):257-63. doi: 10.1111/j.1365-2869.2011.00958.x. Epub 2011 Sep 28. — View Citation

Ferri R, Fulda S, Cosentino FI, Pizza F, Plazzi G. A preliminary quantitative analysis of REM sleep chin EMG in Parkinson's disease with or without REM sleep behavior disorder. Sleep Med. 2012 Jun;13(6):707-13. doi: 10.1016/j.sleep.2012.01.003. Epub 2012 Mar 20. — View Citation

Ferri R, Manconi M, Plazzi G, Bruni O, Vandi S, Montagna P, Ferini-Strambi L, Zucconi M. A quantitative statistical analysis of the submentalis muscle EMG amplitude during sleep in normal controls and patients with REM sleep behavior disorder. J Sleep Res. 2008 Mar;17(1):89-100. doi: 10.1111/j.1365-2869.2008.00631.x. — View Citation

Ferri R, Mogavero MP, Bruni O, Plazzi G, Schenck CH, DelRosso LM. Increased chin muscle tone during all sleep stages in children taking selective serotonin reuptake inhibitor antidepressants and in children with narcolepsy type 1. Sleep. 2021 Nov 12;44(11):zsab147. doi: 10.1093/sleep/zsab147. — View Citation

Ferri R, Rundo F, Manconi M, Plazzi G, Bruni O, Oldani A, Ferini-Strambi L, Zucconi M. Improved computation of the atonia index in normal controls and patients with REM sleep behavior disorder. Sleep Med. 2010 Oct;11(9):947-9. doi: 10.1016/j.sleep.2010.06.003. — View Citation

Figorilli M, Lanza G, Congiu P, Lecca R, Casaglia E, Mogavero MP, Puligheddu M, Ferri R. Neurophysiological Aspects of REM Sleep Behavior Disorder (RBD): A Narrative Review. Brain Sci. 2021 Nov 30;11(12):1588. doi: 10.3390/brainsci11121588. — View Citation

Lanza G, Arico D, Lanuzza B, Cosentino FII, Tripodi M, Giardina F, Bella R, Puligheddu M, Pennisi G, Ferri R, Pennisi M. Facilitatory/inhibitory intracortical imbalance in REM sleep behavior disorder: early electrophysiological marker of neurodegeneration? Sleep. 2020 Mar 12;43(3):zsz242. doi: 10.1093/sleep/zsz242. — View Citation

Lanza G, Cosentino FII, Lanuzza B, Tripodi M, Arico D, Figorilli M, Puligheddu M, Fisicaro F, Bella R, Ferri R, Pennisi M. Reduced Intracortical Facilitation to TMS in Both Isolated REM Sleep Behavior Disorder (RBD) and Early Parkinson's Disease with RBD. J Clin Med. 2022 Apr 20;11(9):2291. doi: 10.3390/jcm11092291. — View Citation

Lee K, Baron K, Soca R, Attarian H. The Prevalence and Characteristics of REM Sleep without Atonia (RSWA) in Patients Taking Antidepressants. J Clin Sleep Med. 2016 Mar;12(3):351-5. doi: 10.5664/jcsm.5582. — View Citation

Miglis MG, Adler CH, Antelmi E, Arnaldi D, Baldelli L, Boeve BF, Cesari M, Dall'Antonia I, Diederich NJ, Doppler K, Dusek P, Ferri R, Gagnon JF, Gan-Or Z, Hermann W, Hogl B, Hu MT, Iranzo A, Janzen A, Kuzkina A, Lee JY, Leenders KL, Lewis SJG, Liguori C, — View Citation

Miyamoto M, Miyamoto T, Kubo J, Yokota N, Hirata K, Sato T. Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H-MRS). Psychiatry Clin Neurosci. 2000 Jun;54(3):350-1. doi: 10.1046/j.1440-1819.2000.00710.x. — View Citation

Mondello S, Kobeissy F, Mechref Y, Zhao J, Talih FR, Cosentino F, Antelmi E, Moresco M, Plazzi G, Ferri R. Novel biomarker signatures for idiopathic REM sleep behavior disorder: A proteomic and system biology approach. Neurology. 2018 Oct 30;91(18):e1710-e1715. doi: 10.1212/WNL.0000000000006439. Epub 2018 Sep 26. Erratum In: Neurology. 2018 Dec 11;91(24):1117. — View Citation

Postuma RB, Gagnon JF, Tuineaig M, Bertrand JA, Latreille V, Desjardins C, Montplaisir JY. Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal? Sleep. 2013 Nov 1;36(11):1579-85. doi: 10.5665/sleep.3102. — View Citation

Postuma RB, Iranzo A, Hu M, Hogl B, Boeve BF, Manni R, Oertel WH, Arnulf I, Ferini-Strambi L, Puligheddu M, Antelmi E, Cochen De Cock V, Arnaldi D, Mollenhauer B, Videnovic A, Sonka K, Jung KY, Kunz D, Dauvilliers Y, Provini F, Lewis SJ, Buskova J, Pavlova M, Heidbreder A, Montplaisir JY, Santamaria J, Barber TR, Stefani A, St Louis EK, Terzaghi M, Janzen A, Leu-Semenescu S, Plazzi G, Nobili F, Sixel-Doering F, Dusek P, Bes F, Cortelli P, Ehgoetz Martens K, Gagnon JF, Gaig C, Zucconi M, Trenkwalder C, Gan-Or Z, Lo C, Rolinski M, Mahlknecht P, Holzknecht E, Boeve AR, Teigen LN, Toscano G, Mayer G, Morbelli S, Dawson B, Pelletier A. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019 Mar 1;142(3):744-759. doi: 10.1093/brain/awz030. — View Citation

Puligheddu M, Figorilli M, Serra A, Laccu I, Congiu P, Tamburrino L, de Natale ER, Ginatempo F, Deriu F, Loi G, Fantini ML, Schenck CH, Ferri R. REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder. Sleep. 2019 Sep 6;42(9):zsz128. doi: 10.1093/sleep/zsz128. — View Citation

Schenck CH, Montplaisir JY, Frauscher B, Hogl B, Gagnon JF, Postuma R, Sonka K, Jennum P, Partinen M, Arnulf I, Cochen de Cock V, Dauvilliers Y, Luppi PH, Heidbreder A, Mayer G, Sixel-Doring F, Trenkwalder C, Unger M, Young P, Wing YK, Ferini-Strambi L, Ferri R, Plazzi G, Zucconi M, Inoue Y, Iranzo A, Santamaria J, Bassetti C, Moller JC, Boeve BF, Lai YY, Pavlova M, Saper C, Schmidt P, Siegel JM, Singer C, St Louis E, Videnovic A, Oertel W. Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group. Sleep Med. 2013 Aug;14(8):795-806. doi: 10.1016/j.sleep.2013.02.016. Epub 2013 Jul 22. Erratum In: Sleep Med. 2014 Jan;15(1):157. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Enrollment of 600 subjects without and with RSWA.	Constitution of a large cohort of 600 subjects without and with RSWA.	18 months