The Effects of Tasimelteon in Participants With REM Behavior Disorder (RBD)

NCT05922995 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: 2022P001873
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the effects of a daily single oral dose of 20 mg tasimelteon compared to baseline on events of dream enactment on patients with REM Behavior Disorder, as measured by a daily log. To assess the effects of 20 mg tasimelteon compared to baseline on insomnia= symptoms, as measured by validated questionnaires (Insomnia Severity Index \[ISI\], Pittsburgh Sleep Quality Inventory \[PSQI\], Epworth Sleepiness Scale \[ESS\], Clinical Global Impression of Change Scale (CGI-C), Patient Global Impression of Change Scale (PGI-C)) as well as rest/activity pattern from actigraphy.

• To assess the effects of 20 mg tasimelteon on patients who have a reduced or aberrant melatonin secretion compared to normal secretion by measuring salivary DLMO at baseline and correlating with the degree of change in RBD symptoms by end of the study.
• To assess for any role a patient's unique genome may play in their response to tasimelteon; obtained via whole genome sequencing.
• To assess the safety and tolerability of a daily single oral dose of 20 mg tasimelteon.

Conditions

REM Behavior Disorder

Keywords

REM behavior disorder; RBD; REM disorder

Outcome Measures

Primary Outcomes (4)

• Daily Sleep Diary - Visual Fill-In

  The daily sleep diary contains a diagram similar to a calendar that the participant can track their intake of caffeine, medicine, and alcohol, if they exercised, when they went to bed, fell asleep, or took a nap, and when they woke up. All recordings will be measured as number of events/time of day.

  Daily for 8 weeks (both baseline and treatment phases)

• Daily Sleep Diary - Time Keeping

  The daily sleep diary also contains a series of questions. Some of them ask the participant to record the time the diary is completed, the time they took the study drug, and the time that they think they had a dream reenactment event. All of these will be recorded in 24:00 format.

  Daily for 8 weeks (both baseline and treatment phases)

• Daily Sleep Diary - Sleep Questions

  The daily sleep diary also asks participants subjective questions like did you sleep last night, did you wake up naturally, and did you take the study drug last night? These will be recorded as yes/no responses.

  Daily for 8 weeks (both baseline and treatment phases)

• Daily Sleep Diary - Dream Enactment

  The daily sleep diary also asks participants to recall how many dream enactments they had the previous night if any at all. This will be recorded as a numerical value.

  Daily for 8 weeks (both baseline and treatment phases)

Secondary Outcomes (1)

• Clinical Global Impression of Change

  1 Month after study

Study Arms (1)

Treatment Phase

EXPERIMENTAL

Tasimelteon will be administered in 20 mg capsules on a nightly basis for 4 weeks during the treatment phase.

Drug: Tasimelteon

Interventions

Tasimelteon DRUG

20 mg capsules taken on a nightly basis

Also known as: Hetlioz

Treatment Phase

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of REM sleep behavior disorder, confirmed polysomnography
• Ability to participate in the trial

You may not qualify if:

• Contraindication to tasimelteon
• medical or psychiatric conditions that limit ability to participate or increase risk to the individual

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Vanda Pharmaceuticals: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (28)

• Haba-Rubio J, Frauscher B, Marques-Vidal P, Toriel J, Tobback N, Andries D, Preisig M, Vollenweider P, Postuma R, Heinzer R. Prevalence and determinants of rapid eye movement sleep behavior disorder in the general population. Sleep. 2018 Feb 1;41(2):zsx197. doi: 10.1093/sleep/zsx197.

  PMID: 29216391 BACKGROUND

• Chiu HF, Wing YK, Lam LC, Li SW, Lum CM, Leung T, Ho CK. Sleep-related injury in the elderly--an epidemiological study in Hong Kong. Sleep. 2000 Jun 15;23(4):513-7.

  PMID: 10875558 BACKGROUND

• Boeve BF, Molano JR, Ferman TJ, Lin SC, Bieniek K, Tippmann-Peikert M, Boot B, St Louis EK, Knopman DS, Petersen RC, Silber MH. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. J Clin Sleep Med. 2013 May 15;9(5):475-80. doi: 10.5664/jcsm.2670.

  PMID: 23674939 BACKGROUND

• Stiasny-Kolster K, Mayer G, Schafer S, Moller JC, Heinzel-Gutenbrunner M, Oertel WH. The REM sleep behavior disorder screening questionnaire--a new diagnostic instrument. Mov Disord. 2007 Dec;22(16):2386-93. doi: 10.1002/mds.21740.

  PMID: 17894337 BACKGROUND

• Postuma RB, Gagnon JF, Montplaisir J. Rapid eye movement sleep behavior disorder as a biomarker for neurodegeneration: the past 10 years. Sleep Med. 2013 Aug;14(8):763-7. doi: 10.1016/j.sleep.2012.09.001. Epub 2012 Oct 8.

  PMID: 23058689 BACKGROUND

• Marion MH, Qurashi M, Marshall G, Foster O. Is REM sleep behaviour disorder (RBD) a risk factor of dementia in idiopathic Parkinson's disease? J Neurol. 2008 Feb;255(2):192-6. doi: 10.1007/s00415-008-0629-9. Epub 2008 Jan 29.

  PMID: 18217187 BACKGROUND

• Ma C, Pavlova M, Liu Y, Liu Y, Huangfu C, Wu S, Gao X. Probable REM sleep behavior disorder and risk of stroke: A prospective study. Neurology. 2017 May 9;88(19):1849-1855. doi: 10.1212/WNL.0000000000003902. Epub 2017 Apr 7.

  PMID: 28389588 BACKGROUND

• Nightingale S, Orgill JC, Ebrahim IO, de Lacy SF, Agrawal S, Williams AJ. The association between narcolepsy and REM behavior disorder (RBD). Sleep Med. 2005 May;6(3):253-8. doi: 10.1016/j.sleep.2004.11.007.

  PMID: 15854856 BACKGROUND

• Boeve BF. REM sleep behavior disorder: Updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci. 2010 Jan;1184:15-54. doi: 10.1111/j.1749-6632.2009.05115.x.

  PMID: 20146689 BACKGROUND

• Czeisler CA, Zimmerman JC, Ronda JM, Moore-Ede MC, Weitzman ED. Timing of REM sleep is coupled to the circadian rhythm of body temperature in man. Sleep. 1980;2(3):329-46.

  PMID: 7403736 BACKGROUND

• Dijk DJ, Czeisler CA. Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. J Neurosci. 1995 May;15(5 Pt 1):3526-38. doi: 10.1523/JNEUROSCI.15-05-03526.1995.

  PMID: 7751928 BACKGROUND

• Carskadon MA, Dement WC. Sleep studies on a 90-minute day. Electroencephalogr Clin Neurophysiol. 1975 Aug;39(2):145-55. doi: 10.1016/0013-4694(75)90004-8.

  PMID: 50211 BACKGROUND

• 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.

  PMID: 26446247 BACKGROUND

• Arnaldi D, Fama F, De Carli F, Morbelli S, Ferrara M, Picco A, Accardo J, Primavera A, Sambuceti G, Nobili F. The Role of the Serotonergic System in REM Sleep Behavior Disorder. Sleep. 2015 Sep 1;38(9):1505-9. doi: 10.5665/sleep.5000.

  PMID: 25845692 BACKGROUND

• Liu J, Clough SJ, Hutchinson AJ, Adamah-Biassi EB, Popovska-Gorevski M, Dubocovich ML. MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective. Annu Rev Pharmacol Toxicol. 2016;56:361-83. doi: 10.1146/annurev-pharmtox-010814-124742. Epub 2015 Oct 23.

  PMID: 26514204 BACKGROUND

• Adi N, Mash DC, Ali Y, Singer C, Shehadeh L, Papapetropoulos S. Melatonin MT1 and MT2 receptor expression in Parkinson's disease. Med Sci Monit. 2010 Feb;16(2):BR61-7.

  PMID: 20110911 BACKGROUND

• Dubocovich ML, Markowska M. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine. 2005 Jul;27(2):101-10. doi: 10.1385/ENDO:27:2:101.

  PMID: 16217123 BACKGROUND

• Lee CH, Yoo KY, Choi JH, Park OK, Hwang IK, Kwon YG, Kim YM, Won MH. Melatonin's protective action against ischemic neuronal damage is associated with up-regulation of the MT2 melatonin receptor. J Neurosci Res. 2010 Sep;88(12):2630-40. doi: 10.1002/jnr.22430.

  PMID: 20544829 BACKGROUND

• Kunz D, Bes F. Melatonin effects in a patient with severe REM sleep behavior disorder: case report and theoretical considerations. Neuropsychobiology. 1997;36(4):211-4. doi: 10.1159/000119383.

  PMID: 9396020 BACKGROUND

• Takeuchi N, Uchimura N, Hashizume Y, Mukai M, Etoh Y, Yamamoto K, Kotorii T, Ohshima H, Ohshima M, Maeda H. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci. 2001 Jun;55(3):267-9. doi: 10.1046/j.1440-1819.2001.00854.x.

  PMID: 11422870 BACKGROUND

• Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003 Jul;4(4):281-4. doi: 10.1016/s1389-9457(03)00072-8.

  PMID: 14592300 BACKGROUND

• Kunz D, Bes F. Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord. 1999 May;14(3):507-11. doi: 10.1002/1531-8257(199905)14:33.0.co;2-8.

  PMID: 10348479 BACKGROUND

• McGrane IR, Leung JG, St Louis EK, Boeve BF. Melatonin therapy for REM sleep behavior disorder: a critical review of evidence. Sleep Med. 2015 Jan;16(1):19-26. doi: 10.1016/j.sleep.2014.09.011. Epub 2014 Oct 13.

  PMID: 25454845 BACKGROUND

• Nomura T, Kawase S, Watanabe Y, Nakashima K. Use of ramelteon for the treatment of secondary REM sleep behavior disorder. Intern Med. 2013;52(18):2123-6. doi: 10.2169/internalmedicine.52.9179.

  PMID: 24042525 BACKGROUND

• Esaki Y, Kitajima T, Koike S, Fujishiro H, Iwata Y, Tsuchiya A, Hirose M, Iwata N. An Open-Labeled Trial of Ramelteon in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. J Clin Sleep Med. 2016 May 15;12(5):689-93. doi: 10.5664/jcsm.5796.

  PMID: 26857053 BACKGROUND

• Kashihara K, Nomura T, Maeda T, Tsuboi Y, Mishima T, Takigawa H, Nakashima K. Beneficial Effects of Ramelteon on Rapid Eye Movement Sleep Behavior Disorder Associated with Parkinson's Disease - Results of a Multicenter Open Trial. Intern Med. 2016;55(3):231-6. doi: 10.2169/internalmedicine.55.5464. Epub 2016 Feb 1.

  PMID: 26831015 BACKGROUND

• Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB. Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials. Lancet. 2009 Feb 7;373(9662):482-91. doi: 10.1016/S0140-6736(08)61812-7. Epub 2008 Dec 4.

  PMID: 19054552 BACKGROUND

• Postuma RB, Arnulf I, Hogl B, Iranzo A, Miyamoto T, Dauvilliers Y, Oertel W, Ju YE, Puligheddu M, Jennum P, Pelletier A, Wolfson C, Leu-Semenescu S, Frauscher B, Miyamoto M, Cochen De Cock V, Unger MM, Stiasny-Kolster K, Fantini ML, Montplaisir JY. A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study. Mov Disord. 2012 Jun;27(7):913-6. doi: 10.1002/mds.25037. Epub 2012 May 30.

  PMID: 22729987 BACKGROUND

MeSH Terms

Conditions

REM Sleep Behavior Disorder

Interventions

tasimelteon

Condition Hierarchy (Ancestors)

REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Study Officials

• Milena Pavlova, M.D.

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: June 28, 2023
• Study Start: September 30, 2023
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)