DIalysis Symptom COntrol-Restless Legs Syndrome Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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DIalysis Symptom COntrol-Restless Legs Syndrome Trial (DISCO-RLS Trial): A Randomized Controlled Trial

Conditions
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End Stage Renal Disease, Restless Legs Syndrome

Intervention / Treatment
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* Drug: Gabapentin
* Drug: Ropinirole
* Drug: Placebo Gabapentin
* Drug: Placebo Ropinirole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gabapentin + Ropinirole<br>Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks. | Drug: Gabapentin<br>* 100 mg capsule<br>* Other names: GD-Gabapentin;Drug: Ropinirole<br>* 0.50 mg capsule<br>* Other names: pms-Ropinirole;|
| Placebo Comparator: Gabapentin + Placebo Ropinirole<br>Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole placebo 0.50 mg capsule, once daily for 4 weeks. | Drug: Gabapentin<br>* 100 mg capsule<br>* Other names: GD-Gabapentin;Drug: Placebo Ropinirole<br>* Placebo capsule<br>* Other names: Placebo;|
| Placebo Comparator: Ropinirole + Placebo Gabapentin<br>Gabapentin placebo 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks. | Drug: Ropinirole<br>* 0.50 mg capsule<br>* Other names: pms-Ropinirole;Drug: Placebo Gabapentin<br>* Placebo capsule<br>* Other names: Placebo;|
| Placebo Comparator: Placebo Gabapentin + Placebo Ropinirole<br>Gabapentin placebo 100 mg capsule, once daily for 4 weeks. Ropinirole placebo 0.50 mg capsule, once daily for 4 weeks. | Drug: Placebo Gabapentin<br>* Placebo capsule<br>* Other names: Placebo;Drug: Placebo Ropinirole<br>* Placebo capsule<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Restless Legs Syndrome Study Group Rating Scale (IRLS) | 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. | 18 weeks (Baseline, Run-In, Follow-up) | 

Secondary Outcome Measures

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