<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03255642</url>
  </required_header>
  <id_info>
    <org_study_id>2017-03-011</org_study_id>
    <nct_id>NCT03255642</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Melatonin and Clonazepam for IRBD</brief_title>
  <official_title>Efficacy and Safety of Melatonin and Rivotril Treatment for Idiopathic Rapid Eye Movement Sleep Disorder: Prospective Randomized Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kyung Hee University Hospital at Gangdong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kyung Hee University Hospital at Gangdong</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aimed to evaluate influence of melatonin or clonazepam treatment on symptom and&#xD;
      polysomnographic parameters in patients with idiopathic REM sleep behavior disorder.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is open-label parallel trial with 4 weeks treatment with slow-release melatonin&#xD;
      (Circadin) or with clonazepam (Rivotril).&#xD;
&#xD;
      Polysomnography, symptom diary and questionnaire (Clinical Global Impression, RBDQ-HK, PSQI,&#xD;
      ESS, SSS, ISI, BDI-II) will be performed before and after 4 weeks of each medications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 9, 2017</start_date>
  <completion_date type="Actual">December 1, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Prospective Randomized Open-label study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Mask treatment arm when analyzing polysomnography.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Automated REM without atonia index</measure>
    <time_frame>4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg</time_frame>
    <description>Percentage seconds with chin EMG amplitude&lt;1uV/ Total REM seconds.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression of RBD symptom severity</measure>
    <time_frame>4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg</time_frame>
    <description>Clinical Global Impression scale score provided by patient and caregiver.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>REM sleep behavior disorder symptom severity</measure>
    <time_frame>4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg</time_frame>
    <description>REM sleep behavior disorder questionnaire-Hong Kong total score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep quality</measure>
    <time_frame>4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg</time_frame>
    <description>Pittsburg Sleep Quality Index total score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression</measure>
    <time_frame>4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg</time_frame>
    <description>Beck depression inventory-II total score</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>REM Sleep Behavior Disorder</condition>
  <arm_group>
    <arm_group_label>Melatonin 2mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4 weeks of 2mg of prolonged release Melatonin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ClonazePAM 0.5 MG</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>4 weeks of 0.5mg of rivotril</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin 2mg</intervention_name>
    <description>4 weeks of 2mg prolonged release melatonin (Circadin)</description>
    <arm_group_label>Melatonin 2mg</arm_group_label>
    <other_name>Circadin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ClonazePAM 0.5 MG</intervention_name>
    <description>4 weeks of 0.5mg clonazepam (Rivotril)</description>
    <arm_group_label>ClonazePAM 0.5 MG</arm_group_label>
    <other_name>Rivotril</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  REM sleep behavior disorder (ICSD-3 criteria)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neurological disorder including epilepsy or stroke&#xD;
&#xD;
          -  History of psychiatric illness&#xD;
&#xD;
          -  Neurodegenerative disease including dementia or parkinsonism.&#xD;
&#xD;
          -  Medication affecting sleep within 1 month&#xD;
&#xD;
          -  Intake of melatonin or clonazepam within 1 week.&#xD;
&#xD;
          -  Unable to complete questionnaires&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Won Chul Shin, M.D. Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>KyungHee University Hospital at Gangdong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kyung Hee University Hospital at Gangdong</name>
      <address>
        <city>Seoul</city>
        <zip>05269</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Ferri R, Marelli S, Ferini-Strambi L, Oldani A, Colli F, Schenck CH, Zucconi M. An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder. Sleep Med. 2013 Jan;14(1):24-9. doi: 10.1016/j.sleep.2012.09.009. Epub 2012 Oct 23.</citation>
    <PMID>23098778</PMID>
  </reference>
  <reference>
    <citation>Kunz D, Mahlberg R. A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep Res. 2010 Dec;19(4):591-6. doi: 10.1111/j.1365-2869.2010.00848.x.</citation>
    <PMID>20561180</PMID>
  </reference>
  <reference>
    <citation>McCarter SJ, Boswell CL, St Louis EK, Dueffert LG, Slocumb N, Boeve BF, Silber MH, Olson EJ, Tippmann-Peikert M. Treatment outcomes in REM sleep behavior disorder. Sleep Med. 2013 Mar;14(3):237-42. doi: 10.1016/j.sleep.2012.09.018. Epub 2013 Jan 23.</citation>
    <PMID>23352028</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25454845</PMID>
  </reference>
  <reference>
    <citation>Nardone R, Golaszewski S, Holler Y, Christova M, Trinka E, Brigo F. Neurophysiological insights into the pathophysiology of REM sleep behavior disorders: a review. Neurosci Res. 2013 Jul;76(3):106-12. doi: 10.1016/j.neures.2013.03.009. Epub 2013 Mar 28.</citation>
    <PMID>23542221</PMID>
  </reference>
  <reference>
    <citation>Iranzo A, Molinuevo JL, Santamaria J, Serradell M, Marti MJ, Valldeoriola F, Tolosa E. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006 Jul;5(7):572-7. doi: 10.1016/S1474-4422(06)70476-8.</citation>
    <PMID>16781987</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>May 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <last_update_submitted>February 18, 2021</last_update_submitted>
  <last_update_submitted_qc>February 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kyung Hee University Hospital at Gangdong</investigator_affiliation>
    <investigator_full_name>Won Chul Shin</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Clonazepam</keyword>
  <keyword>Melatonin</keyword>
  <keyword>Treatment</keyword>
  <keyword>REM Sleep Behavior Disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>REM Sleep Behavior Disorder</mesh_term>
    <mesh_term>Mental Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clonazepam</mesh_term>
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03255642
org study id: 2017-03-011
nct id: NCT03255642
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study aimed to evaluate influence of melatonin or clonazepam treatment on symptom and
      polysomnographic parameters in patients with idiopathic REM sleep behavior disorder.
This study is open-label parallel trial with 4 weeks treatment with slow-release melatonin
      (Circadin) or with clonazepam (Rivotril).

      Polysomnography, symptom diary and questionnaire (Clinical Global Impression, RBDQ-HK, PSQI,
      ESS, SSS, ISI, BDI-II) will be performed before and after 4 weeks of each medications.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective Randomized Open-label study
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Mask treatment arm when analyzing polysomnography.
measure: Automated REM without atonia index
time frame: 4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg
description: Percentage seconds with chin EMG amplitude<1uV/ Total REM seconds.
measure: Clinical Global Impression of RBD symptom severity
time frame: 4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg
description: Clinical Global Impression scale score provided by patient and caregiver.
measure: REM sleep behavior disorder symptom severity
time frame: 4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg
description: REM sleep behavior disorder questionnaire-Hong Kong total score
measure: Sleep quality
time frame: 4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg
description: Pittsburg Sleep Quality Index total score
measure: Depression
time frame: 4 weeks of prolonged release melatonin 2mg or clonazepam 0.5mg
description: Beck depression inventory-II total score
arm group label: Melatonin 2mg
arm group type: Active Comparator
description: 4 weeks of 2mg of prolonged release Melatonin
arm group label: ClonazePAM 0.5 MG
arm group type: Placebo Comparator
description: 4 weeks of 0.5mg of rivotril
intervention type: Drug
intervention name: Melatonin 2mg
description: 4 weeks of 2mg prolonged release melatonin (Circadin)
arm group label: Melatonin 2mg
other name: Circadin
intervention type: Drug
intervention name: ClonazePAM 0.5 MG
description: 4 weeks of 0.5mg clonazepam (Rivotril)
arm group label: ClonazePAM 0.5 MG
other name: Rivotril
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Won Chul Shin, M.D. Ph.D.
role: Principal Investigator
affiliation: KyungHee University Hospital at Gangdong
facility: 
country: Korea, Republic of
citation: Ferri R, Marelli S, Ferini-Strambi L, Oldani A, Colli F, Schenck CH, Zucconi M. An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder. Sleep Med. 2013 Jan;14(1):24-9. doi: 10.1016/j.sleep.2012.09.009. Epub 2012 Oct 23.
PMID: 23098778
citation: Kunz D, Mahlberg R. A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep Res. 2010 Dec;19(4):591-6. doi: 10.1111/j.1365-2869.2010.00848.x.
PMID: 20561180
citation: McCarter SJ, Boswell CL, St Louis EK, Dueffert LG, Slocumb N, Boeve BF, Silber MH, Olson EJ, Tippmann-Peikert M. Treatment outcomes in REM sleep behavior disorder. Sleep Med. 2013 Mar;14(3):237-42. doi: 10.1016/j.sleep.2012.09.018. Epub 2013 Jan 23.
PMID: 23352028
citation: 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
citation: Nardone R, Golaszewski S, Holler Y, Christova M, Trinka E, Brigo F. Neurophysiological insights into the pathophysiology of REM sleep behavior disorders: a review. Neurosci Res. 2013 Jul;76(3):106-12. doi: 10.1016/j.neures.2013.03.009. Epub 2013 Mar 28.
PMID: 23542221
citation: Iranzo A, Molinuevo JL, Santamaria J, Serradell M, Marti MJ, Valldeoriola F, Tolosa E. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006 Jul;5(7):572-7. doi: 10.1016/S1474-4422(06)70476-8.
PMID: 16781987
responsible party type: Principal Investigator
investigator affiliation: Kyung Hee University Hospital at Gangdong
investigator full name: Won Chul Shin
investigator title: Professor
mesh term: REM Sleep Behavior Disorder
mesh term: Mental Disorders
mesh term: Clonazepam
mesh term: Melatonin
sharing ipd: Undecided