<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/NCT03806530</url>
  </required_header>
  <id_info>
    <org_study_id>DISCO_RLS_001</org_study_id>
    <nct_id>NCT03806530</nct_id>
  </id_info>
  <brief_title>DIalysis Symptom COntrol-Restless Legs Syndrome Trial</brief_title>
  <acronym>DISCO-RLS</acronym>
  <official_title>DIalysis Symptom COntrol-Restless Legs Syndrome Trial (DISCO-RLS Trial): A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Population Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Population Health Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The DISCO-RLS Trial is a randomized controlled trial to determine the safety and efficacy of&#xD;
      pharmacologic therapy (ropinirole versus placebo and gabapentin versus placebo) for the&#xD;
      treatment of Restless Legs Syndrome in patients with End Stage Renal Disease requiring&#xD;
      hemodialysis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The DISCO-RLS Trial is a randomized controlled trial to determine whether or not a fixed,&#xD;
      low-dose therapy with ropinirole and/or gabapentin is safe and effective compared to either&#xD;
      alone or placebo for the treatment of Restless Legs Syndrome in patients with End Stage Renal&#xD;
      Disease receiving hemodialysis. DISCO-RLS will randomize a total of 80 participants.&#xD;
      Participants will be randomized to 1 of 8 treatment sequences. Each sequence is composed of 4&#xD;
      periods and in each period participants will receive 1 of 4 possible combinations of study&#xD;
      medications (gabapentin+ropinirole, gabapentin+placebo ropinirole, ropinirole+placebo&#xD;
      gabapentin, placebo gabapentin+placebo ropinirole). Eligible participants will complete a&#xD;
      1-week Run-In period followed by 4 periods of 4 weeks each for a total of 16-week follow-up&#xD;
      after randomization. A final study visit will be completed at the end of the 16 week&#xD;
      follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Actual">July 19, 2022</completion_date>
  <primary_completion_date type="Actual">December 14, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Participants will be randomly allocated to 1 of 8 treatment sequences. Each sequence is composed of 4 periods and in each period participants will receive 1 of 4 possible combinations of study medications (gabapentin+ropinirole, gabapentin+placebo ropinirole, ropinirole+placebo gabapentin, placebo gabapentin+placebo ropinirole).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The study interventions will be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>International Restless Legs Syndrome Study Group Rating Scale (IRLS)</measure>
    <time_frame>18 weeks (Baseline, Run-In, Follow-up)</time_frame>
    <description>The IRLS is a measure of severity of Restless Legs Syndrome. It includes 10 items, measured on a scale of 0-4. A score of 1-10 indicates mild severity, 11-20 indicates moderate severity, 21-30 is severe and 31-40 is very severe. Primary outcome is the difference in IRLS scores for each of the treatment regimens.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Restless Legs Syndrome-6 Scale (RLS-6)</measure>
    <time_frame>18 weeks (Baseline, Run-In, Follow-up)</time_frame>
    <description>The RLS-6 is a measure of severity of Restless Legs Syndrome for the past week. It includes 6 items, measured on a scale of 0-10. Each item is measured from no symptoms (score of 0) to very severe symptoms (score of 10). Secondary outcome is the difference in RLS-6 scores for each of the treatment regimens.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Global Impressions (PGI)</measure>
    <time_frame>18 weeks (Baseline, Run-In, Follow-up)</time_frame>
    <description>The PGI is a measure of Restless Legs Syndrome symptom severity. It includes 1 item, measured on a scale of 1-7. 1 indicates mild severity, 3 indicates moderate severity, 5 is severe and 7 is very severe. Secondary outcome is the difference in PGI scores for each of the treatment regimens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Euro-Quality of Life Scale (EQ-5D-5L)</measure>
    <time_frame>18 weeks (Baseline, Run-In, Follow-up)</time_frame>
    <description>The EQ-5D-5L is a measure of health status. It includes 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and a visual analogue scale of 0-100 (0 being worst health and 100 being best health). The scale is measured by levels. Level 1 indicating no problems, 2 indicating slight problems, 3 indicating moderate problems, 4 indicating severe problems and 5 indicating extreme problems. Secondary outcome is the difference in EQ-5D-5L scores for each of the treatment regimens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of falls, fractures and hospitalizations/emergency room visits due to altered level of consciousness.</measure>
    <time_frame>18 weeks (Baseline, Run-In, Follow-up)</time_frame>
    <description>The total number of falls, fractures, or hospitalization/emergency rooms visits due to confusion/delirium or altered mental state.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>End Stage Renal Disease</condition>
  <condition>Restless Legs Syndrome</condition>
  <arm_group>
    <arm_group_label>Gabapentin + Ropinirole</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gabapentin + Placebo Ropinirole</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole placebo 0.50 mg capsule, once daily for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ropinirole + Placebo Gabapentin</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Gabapentin placebo 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Gabapentin + Placebo Ropinirole</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Gabapentin placebo 100 mg capsule, once daily for 4 weeks. Ropinirole placebo 0.50 mg capsule, once daily for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gabapentin</intervention_name>
    <description>100 mg capsule</description>
    <arm_group_label>Gabapentin + Placebo Ropinirole</arm_group_label>
    <arm_group_label>Gabapentin + Ropinirole</arm_group_label>
    <other_name>GD-Gabapentin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ropinirole</intervention_name>
    <description>0.50 mg capsule</description>
    <arm_group_label>Gabapentin + Ropinirole</arm_group_label>
    <arm_group_label>Ropinirole + Placebo Gabapentin</arm_group_label>
    <other_name>pms-Ropinirole</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Gabapentin</intervention_name>
    <description>Placebo capsule</description>
    <arm_group_label>Placebo Gabapentin + Placebo Ropinirole</arm_group_label>
    <arm_group_label>Ropinirole + Placebo Gabapentin</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Ropinirole</intervention_name>
    <description>Placebo capsule</description>
    <arm_group_label>Gabapentin + Placebo Ropinirole</arm_group_label>
    <arm_group_label>Placebo Gabapentin + Placebo Ropinirole</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater or equal to 18 years&#xD;
&#xD;
          -  Has received at least 90 days of in-center hemodialysis at a frequency at least 3&#xD;
             times weekly&#xD;
&#xD;
          -  RLS defined by 2012 Revised International Restless Legs Syndrome Study Group (IRLSSG)&#xD;
             Diagnostic Criteria for RLS and of moderate severity defined by an IRLS score greater&#xD;
             or equal to 10 with symptoms more than 2 days per week (see IRLS question #7)&#xD;
&#xD;
          -  Provides informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hemoglobin&lt;80g/L in the previous 4 weeks&#xD;
&#xD;
          -  Intolerance to a dopamine agonists (e.g. pramipexole or ropinirole) or alpha 2 delta&#xD;
             ligands (e.g. gabapentin, Neurontin, pregabalin, or Lyrica)&#xD;
&#xD;
          -  Change in medication to treat RLS in previous 4 weeks&#xD;
&#xD;
          -  Current pregnancy&#xD;
&#xD;
          -  Planned kidney transplantation, travel or relocation in the next 6 months&#xD;
&#xD;
          -  Unable to complete RLS symptom and HRQOL measurements due to language barrier or&#xD;
             cognitive impairment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr. Michael Walsh, PhD,FRCPC(C)</last_name>
    <role>Principal Investigator</role>
    <affiliation>Population Health Research Institute, McMaster University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nova Scotia Health Authority</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 2Y9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph's Hamilton Healthcare</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N 4A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 7W9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>September 19, 2022</last_update_submitted>
  <last_update_submitted_qc>September 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychomotor Agitation</mesh_term>
    <mesh_term>Restless Legs Syndrome</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gabapentin</mesh_term>
    <mesh_term>Ropinirole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03806530
org study id: DISCO_RLS_001
nct id: NCT03806530
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The DISCO-RLS Trial is a randomized controlled trial to determine the safety and efficacy of
      pharmacologic therapy (ropinirole versus placebo and gabapentin versus placebo) for the
      treatment of Restless Legs Syndrome in patients with End Stage Renal Disease requiring
      hemodialysis.
The DISCO-RLS Trial is a randomized controlled trial to determine whether or not a fixed,
      low-dose therapy with ropinirole and/or gabapentin is safe and effective compared to either
      alone or placebo for the treatment of Restless Legs Syndrome in patients with End Stage Renal
      Disease receiving hemodialysis. DISCO-RLS will randomize a total of 80 participants.
      Participants will be randomized to 1 of 8 treatment sequences. Each sequence is composed of 4
      periods and in each period participants will receive 1 of 4 possible combinations of study
      medications (gabapentin+ropinirole, gabapentin+placebo ropinirole, ropinirole+placebo
      gabapentin, placebo gabapentin+placebo ropinirole). Eligible participants will complete a
      1-week Run-In period followed by 4 periods of 4 weeks each for a total of 16-week follow-up
      after randomization. A final study visit will be completed at the end of the 16 week
      follow-up.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Participants will be randomly allocated to 1 of 8 treatment sequences. Each sequence is composed of 4 periods and in each period participants will receive 1 of 4 possible combinations of study medications (gabapentin+ropinirole, gabapentin+placebo ropinirole, ropinirole+placebo gabapentin, placebo gabapentin+placebo ropinirole).
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The study interventions will be blinded.
measure: International Restless Legs Syndrome Study Group Rating Scale (IRLS)
time frame: 18 weeks (Baseline, Run-In, Follow-up)
description: The IRLS is a measure of severity of Restless Legs Syndrome. It includes 10 items, measured on a scale of 0-4. A score of 1-10 indicates mild severity, 11-20 indicates moderate severity, 21-30 is severe and 31-40 is very severe. Primary outcome is the difference in IRLS scores for each of the treatment regimens.
measure: Restless Legs Syndrome-6 Scale (RLS-6)
time frame: 18 weeks (Baseline, Run-In, Follow-up)
description: The RLS-6 is a measure of severity of Restless Legs Syndrome for the past week. It includes 6 items, measured on a scale of 0-10. Each item is measured from no symptoms (score of 0) to very severe symptoms (score of 10). Secondary outcome is the difference in RLS-6 scores for each of the treatment regimens.
measure: Patient Global Impressions (PGI)
time frame: 18 weeks (Baseline, Run-In, Follow-up)
description: The PGI is a measure of Restless Legs Syndrome symptom severity. It includes 1 item, measured on a scale of 1-7. 1 indicates mild severity, 3 indicates moderate severity, 5 is severe and 7 is very severe. Secondary outcome is the difference in PGI scores for each of the treatment regimens
measure: Euro-Quality of Life Scale (EQ-5D-5L)
time frame: 18 weeks (Baseline, Run-In, Follow-up)
description: The EQ-5D-5L is a measure of health status. It includes 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression) and a visual analogue scale of 0-100 (0 being worst health and 100 being best health). The scale is measured by levels. Level 1 indicating no problems, 2 indicating slight problems, 3 indicating moderate problems, 4 indicating severe problems and 5 indicating extreme problems. Secondary outcome is the difference in EQ-5D-5L scores for each of the treatment regimens
measure: Incidence of falls, fractures and hospitalizations/emergency room visits due to altered level of consciousness.
time frame: 18 weeks (Baseline, Run-In, Follow-up)
description: The total number of falls, fractures, or hospitalization/emergency rooms visits due to confusion/delirium or altered mental state.
arm group label: Gabapentin + Ropinirole
arm group type: Active Comparator
description: Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks.
arm group label: Gabapentin + Placebo Ropinirole
arm group type: Placebo Comparator
description: Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole placebo 0.50 mg capsule, once daily for 4 weeks.
arm group label: Ropinirole + Placebo Gabapentin
arm group type: Placebo Comparator
description: Gabapentin placebo 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks.
arm group label: Placebo Gabapentin + Placebo Ropinirole
arm group type: Placebo Comparator
description: Gabapentin placebo 100 mg capsule, once daily for 4 weeks. Ropinirole placebo 0.50 mg capsule, once daily for 4 weeks.
intervention type: Drug
intervention name: Gabapentin
description: 100 mg capsule
arm group label: Gabapentin + Placebo Ropinirole
arm group label: Gabapentin + Ropinirole
other name: GD-Gabapentin
intervention type: Drug
intervention name: Ropinirole
description: 0.50 mg capsule
arm group label: Gabapentin + Ropinirole
arm group label: Ropinirole + Placebo Gabapentin
other name: pms-Ropinirole
intervention type: Drug
intervention name: Placebo Gabapentin
description: Placebo capsule
arm group label: Placebo Gabapentin + Placebo Ropinirole
arm group label: Ropinirole + Placebo Gabapentin
other name: Placebo
intervention type: Drug
intervention name: Placebo Ropinirole
description: Placebo capsule
arm group label: Gabapentin + Placebo Ropinirole
arm group label: Placebo Gabapentin + Placebo Ropinirole
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dr. Michael Walsh, PhD,FRCPC(C)
role: Principal Investigator
affiliation: Population Health Research Institute, McMaster University
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Psychomotor Agitation
mesh term: Restless Legs Syndrome
mesh term: Kidney Failure, Chronic
mesh term: Syndrome
mesh term: Gabapentin
mesh term: Ropinirole
sharing ipd: No