DIalysis Symptom COntrol-Restless Legs Syndrome Trial (DISCO-RLS)

• ClinicalTrials.gov Identifier: NCT03806530
• Recruitment Status: Completed
• First Posted: January 16, 2019
• Last Update Posted: September 21, 2022
• Sponsor: Population Health Research Institute
• Information provided by (Responsible Party): Population Health Research Institute

Tracking Information

• First Submitted Date: January 14, 2019
• First Posted Date: January 16, 2019
• Last Update Posted Date: September 21, 2022
• Actual Study Start Date: May 1, 2019
• Actual Primary Completion Date: December 14, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 26, 2019)

International Restless Legs Syndrome Study Group Rating Scale (IRLS) [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]

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.

Original Primary Outcome Measures (submitted: January 14, 2019)

International Restless Legs Syndrome (IRLS) Score [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]

The difference in IRLS scores for each of the treatment regimens.

Current Secondary Outcome Measures (submitted: November 26, 2019)

• Restless Legs Syndrome-6 Scale (RLS-6) [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]
  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.
• Patient Global Impressions (PGI) [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]
  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
• Euro-Quality of Life Scale (EQ-5D-5L) [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]
  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
• Incidence of falls, fractures and hospitalizations/emergency room visits due to altered level of consciousness. [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]
  The total number of falls, fractures, or hospitalization/emergency rooms visits due to confusion/delirium or altered mental state.

Original Secondary Outcome Measures (submitted: January 14, 2019)

• Restless Legs Syndrome-6 Scale (RLS-6) [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]
  The difference in RLS-6 scores for each of the treatment regimens.
• Patient Global Impressions (PGI) [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]
  The difference in PGI scores for each of the treatment regimens
• EQ-5D-5L Score [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]
  The difference in EQ-5D-5L scores for each of the treatment regimens
• Incidence of falls, fractures and hospitalizations/emergency room visits due to altered level of consciousness. [ Time Frame: 18 weeks (Baseline, Run-In, Follow-up) ]
  The total number of falls, fractures, or hospitalization/emergency rooms visits due to confusion/delirium or altered mental state.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: DIalysis Symptom COntrol-Restless Legs Syndrome Trial
• Official Title: DIalysis Symptom COntrol-Restless Legs Syndrome Trial (DISCO-RLS Trial): A Randomized Controlled Trial
• Brief Summary: 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.
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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).

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The study interventions will be blinded.

Primary Purpose: Treatment

Condition

• End Stage Renal Disease
• Restless Legs Syndrome

Intervention

• Drug: Gabapentin
  100 mg capsule
  Other Name: GD-Gabapentin
• Drug: Ropinirole
  0.50 mg capsule
  Other Name: pms-Ropinirole
• Drug: Placebo Gabapentin
  Placebo capsule
  Other Name: Placebo
• Drug: Placebo Ropinirole
  Placebo capsule
  Other Name: Placebo

Study Arms

• Active Comparator: Gabapentin + Ropinirole
  Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks.
  Interventions:

  • Drug: Gabapentin
  • Drug: Ropinirole
• Placebo Comparator: Gabapentin + Placebo Ropinirole
  Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole placebo 0.50 mg capsule, once daily for 4 weeks.
  Interventions:

  • Drug: Gabapentin
  • Drug: Placebo Ropinirole
• Placebo Comparator: Ropinirole + Placebo Gabapentin
  Gabapentin placebo 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks.
  Interventions:

  • Drug: Ropinirole
  • Drug: Placebo Gabapentin
• Placebo Comparator: Placebo Gabapentin + Placebo Ropinirole
  Gabapentin placebo 100 mg capsule, once daily for 4 weeks. Ropinirole placebo 0.50 mg capsule, once daily for 4 weeks.
  Interventions:

  • Drug: Placebo Gabapentin
  • Drug: Placebo Ropinirole

• Publications *: Collister D, Pohl K, Herrington G, Lee SF, Rabbat C, Tennankore K, Zimmermann D, Tangri N, Wald R, Manns B, Suri RS, Nadeau-Fredette AC, Goupil R, Silver SA, Walsh M. The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) Trial: A Protocol for a Randomized, Crossover, Placebo-Controlled Blinded Trial. Can J Kidney Health Dis. 2020 Nov 26;7:2054358120968959. doi: 10.1177/2054358120968959. eCollection 2020.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 19, 2022): 52
• Original Estimated Enrollment (submitted: January 14, 2019): 80
• Actual Study Completion Date: July 19, 2022
• Actual Primary Completion Date: December 14, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age greater or equal to 18 years
• Has received at least 90 days of in-center hemodialysis at a frequency at least 3 times weekly
• RLS defined by 2012 Revised International Restless Legs Syndrome Study Group (IRLSSG) Diagnostic Criteria for RLS and of moderate severity defined by an IRLS score greater or equal to 10 with symptoms more than 2 days per week (see IRLS question #7)
• Provides informed consent

Exclusion Criteria:

• Hemoglobin<80g/L in the previous 4 weeks
• Intolerance to a dopamine agonists (e.g. pramipexole or ropinirole) or alpha 2 delta ligands (e.g. gabapentin, Neurontin, pregabalin, or Lyrica)
• Change in medication to treat RLS in previous 4 weeks
• Current pregnancy
• Planned kidney transplantation, travel or relocation in the next 6 months
• Unable to complete RLS symptom and HRQOL measurements due to language barrier or cognitive impairment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT03806530
• Other Study ID Numbers: DISCO_RLS_001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Population Health Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Population Health Research Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dr. Michael Walsh, PhD,FRCPC(C); Population Health Research Institute, McMaster University

• PRS Account: Population Health Research Institute
• Verification Date: September 2022