<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/NCT03265951</url>
  </required_header>
  <id_info>
    <org_study_id>RF-1070471</org_study_id>
    <nct_id>NCT03265951</nct_id>
  </id_info>
  <brief_title>Ramelteon for Complex Insomnia in Veterans With PTSD</brief_title>
  <acronym>DORMI</acronym>
  <official_title>A Pilot, Randomized, Double-blind, Placebo Controlled, Trial of Ramelteon for CPAP Non-Adherent Veterans With PTSD and Complex Insomnia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>State University of New York at Buffalo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The VA Western New York Healthcare System</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>State University of New York at Buffalo</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      Obstructive sleep apnea is commonly reported in Veterans with post-traumatic stress disorder,&#xD;
      which can potentiate symptoms of anxiety and depression, daytime symptoms and worsen&#xD;
      nightmares. Continuous positive airway pressure is the most effective therapy but adherence&#xD;
      to treatment is suboptimal. The overarching theme of the proposal is to compare usual care to&#xD;
      Ramelteon, in a randomized, clinical trial, investigating the effectiveness of physiological&#xD;
      versus pharmacological intervention on sleep quality of life, insomnia severity and CPAP&#xD;
      adherence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite the overall improvement in PTSD symptomatology with CPAP therapy, adherence to CPAP&#xD;
      is far worse in Veterans with PTSD (41%) compared to the general population with OSA (70%).&#xD;
      Among the factors associated with CPAP non-adherence is the coexistence of insomnia. Complex&#xD;
      insomnia defined as the coexistence of comorbid insomnia ans OSA is a frequent diagnosis in&#xD;
      military personnel with combat exposure. Similar to prior reports of patients with OSA&#xD;
      without PTSD, comorbid insomnia can create a barrier to CPAP therapy. Ramelteon (TAK-375),&#xD;
      approved by the Food and Drug Administration for the treatment of insomnia with sleep onset&#xD;
      abnormalities, is a neurohormone that functions as a melatonin receptor agonist targeting the&#xD;
      MT1 and MT2 receptors located in the suprachiasmatic nucleus of the hypothalamus which&#xD;
      regulates the circadian rhythm of the 24-hour sleep-wake cycle.The goal is to test the&#xD;
      hypothesis that the administration of insomnia therapy-ramelteon- significantly improves&#xD;
      treatment outcomes in Veterans with PTSD and complex insomnia compared with placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of response&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">September 30, 2019</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pittsburgh Sleep Quality Index</measure>
    <time_frame>12 weeks post randomization</time_frame>
    <description>Quality of life</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PCL-5</measure>
    <time_frame>12 weeks post randomization</time_frame>
    <description>PTSD Checklist</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ISI</measure>
    <time_frame>12 weeks post randomization</time_frame>
    <description>Insomnia Severity Index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CPAP adherence</measure>
    <time_frame>12 weeks post randomization</time_frame>
    <description>CPAP adherence</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Insomnia</condition>
  <arm_group>
    <arm_group_label>Ramelteon</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ramelteon 8 mg po at bedtime</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual care</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>education brochure about sleep hygiene</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ramelteon</intervention_name>
    <description>8 mg once daily administered within 30 minutes of bedtime</description>
    <arm_group_label>Ramelteon</arm_group_label>
    <other_name>Rozerem</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Usual Care</intervention_name>
    <description>education brochure about sleep hygiene</description>
    <arm_group_label>Usual care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years and ≤70 years old&#xD;
&#xD;
          -  Diagnosis of PTSD as determined by the intake conducted through the PTSD Clinic or the&#xD;
             Mental Health Clinic&#xD;
&#xD;
          -  Documented obstructive sleep apnea by polysomnography (AHI≥5 or more/hour)&#xD;
&#xD;
          -  CPAP non adherence defined as less than 70% of nights with &gt;4h CPAP use despite&#xD;
             addressing modifiable barriers for CPAP adherence&#xD;
&#xD;
          -  Psychotherapeutic treatment stable for at least 4 weeks prior to randomization&#xD;
&#xD;
          -  Capable of giving informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical:&#xD;
&#xD;
               -  Acute or unstable chronic medical illness&#xD;
&#xD;
               -  History of narcolepsy and/or cataplexy Use of any of these medications:&#xD;
                  Fluvoxamine, fluconazole (Diflucan), itraconazole (Sporanox), and ketoconazole&#xD;
                  (Nizoral); cimetidine (Tagamet); clarithromycin (Biaxin); fluoroquinolones&#xD;
                  including ciprofloxacin, levofloxacin (Levaquin), moxifloxacin (Avelox),&#xD;
                  norfloxacin (Noroxin), ofloxacin (Floxin), others; HIV protease inhibitors&#xD;
                  including indinavir (Crixivan), nelfinavir (Viracept), and ritonavir (Norvir, in&#xD;
                  Kaletra); nefazodone; rifampin&#xD;
&#xD;
               -  Treatment for seizure disorders&#xD;
&#xD;
               -  Pregnant or lactating&#xD;
&#xD;
               -  History of clinically significant hepatic impairment&#xD;
&#xD;
               -  History of hypersensitivity, intolerance, or contraindication to ramelteon&#xD;
&#xD;
               -  Unwilling to try or use CPAP&#xD;
&#xD;
        Psychiatric/Behavioral:&#xD;
&#xD;
          -  Diagnosis of current schizophrenia or schizoaffective disorder&#xD;
&#xD;
          -  Diagnosis of a substance dependence/abuse disorder in the past year&#xD;
&#xD;
          -  Severe psychiatric instability or severe situational life crises, including evidence&#xD;
             of being actively suicidal or homicidal, or any behavior which poses an immediate&#xD;
             danger to patient or others&#xD;
&#xD;
          -  Diagnosis of bipolar disorder&#xD;
&#xD;
          -  Consumption of more than two alcoholic beverages per night&#xD;
&#xD;
          -  Receiving behavioral or pharmacological treatment for insomnia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ali El Solh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The VA Western New York</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Veterans Affairs Medical Center in Buffalo</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>April 8, 2021</last_update_submitted>
  <last_update_submitted_qc>April 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>State University of New York at Buffalo</investigator_affiliation>
    <investigator_full_name>Ali El Solh</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>sleep apnea, PTSD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
  </condition_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/NCT03265951
org study id: RF-1070471
nct id: NCT03265951
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Obstructive sleep apnea is commonly reported in Veterans with post-traumatic stress disorder,
      which can potentiate symptoms of anxiety and depression, daytime symptoms and worsen
      nightmares. Continuous positive airway pressure is the most effective therapy but adherence
      to treatment is suboptimal. The overarching theme of the proposal is to compare usual care to
      Ramelteon, in a randomized, clinical trial, investigating the effectiveness of physiological
      versus pharmacological intervention on sleep quality of life, insomnia severity and CPAP
      adherence.
Despite the overall improvement in PTSD symptomatology with CPAP therapy, adherence to CPAP
      is far worse in Veterans with PTSD (41%) compared to the general population with OSA (70%).
      Among the factors associated with CPAP non-adherence is the coexistence of insomnia. Complex
      insomnia defined as the coexistence of comorbid insomnia ans OSA is a frequent diagnosis in
      military personnel with combat exposure. Similar to prior reports of patients with OSA
      without PTSD, comorbid insomnia can create a barrier to CPAP therapy. Ramelteon (TAK-375),
      approved by the Food and Drug Administration for the treatment of insomnia with sleep onset
      abnormalities, is a neurohormone that functions as a melatonin receptor agonist targeting the
      MT1 and MT2 receptors located in the suprachiasmatic nucleus of the hypothalamus which
      regulates the circadian rhythm of the 24-hour sleep-wake cycle.The goal is to test the
      hypothesis that the administration of insomnia therapy-ramelteon- significantly improves
      treatment outcomes in Veterans with PTSD and complex insomnia compared with placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Pittsburgh Sleep Quality Index
time frame: 12 weeks post randomization
description: Quality of life
measure: PCL-5
time frame: 12 weeks post randomization
description: PTSD Checklist
measure: ISI
time frame: 12 weeks post randomization
description: Insomnia Severity Index
measure: CPAP adherence
time frame: 12 weeks post randomization
description: CPAP adherence
arm group label: Ramelteon
arm group type: Active Comparator
description: Ramelteon 8 mg po at bedtime
arm group label: Usual care
arm group type: Placebo Comparator
description: education brochure about sleep hygiene
intervention type: Drug
intervention name: Ramelteon
description: 8 mg once daily administered within 30 minutes of bedtime
arm group label: Ramelteon
other name: Rozerem
intervention type: Other
intervention name: Usual Care
description: education brochure about sleep hygiene
arm group label: Usual care
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Ali El Solh, MD
role: Principal Investigator
affiliation: The VA Western New York
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: State University of New York at Buffalo
investigator full name: Ali El Solh
investigator title: Principal Investigator
mesh term: Sleep Initiation and Maintenance Disorders
sharing ipd: Undecided