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

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

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.

Study Overview

• Status: Completed
• Conditions: Restless Legs Syndrome; End Stage Renal Disease
• Intervention / Treatment: Drug: Gabapentin; Drug: Ropinirole; Drug: Placebo Ropinirole; Drug: Placebo Gabapentin

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
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Hamilton Healthcare
    • Ottawa, Ontario, Canada, K1H 7W9
      • The Ottawa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Gabapentin + Ropinirole; Gabapentin 100 mg capsule, once daily for 4 weeks. Ropinirole 0.50 mg capsule, once daily for 4 weeks.	Drug: Gabapentin; 100 mg capsule; Other Names: GD-Gabapentin; Drug: Ropinirole; 0.50 mg capsule; Other Names: pms-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.	Drug: Gabapentin; 100 mg capsule; Other Names: GD-Gabapentin; Drug: Placebo Ropinirole; Placebo capsule; Other Names: Placebo
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.	Drug: Ropinirole; 0.50 mg capsule; Other Names: pms-Ropinirole; Drug: Placebo Gabapentin; Placebo capsule; Other Names: Placebo
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.	Drug: Placebo Ropinirole; Placebo capsule; Other Names: Placebo; Drug: Placebo Gabapentin; Placebo capsule; Other Names: Placebo

What is the study measuring?

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)

Collaborators and Investigators

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

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2019
• Primary Completion (ACTUAL): December 14, 2021
• Study Completion (ACTUAL): July 19, 2022

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 14, 2019
• First Posted (ACTUAL): January 16, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Kidney Diseases; Urologic Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Renal Insufficiency; Dyskinesias; Psychomotor Disorders; Parasomnias; Renal Insufficiency, Chronic; Syndrome; Psychomotor Agitation; Restless Legs Syndrome; Kidney Failure, Chronic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agonists; Dopamine Agents; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Gabapentin; Ropinirole
• Other Study ID Numbers: DISCO_RLS_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No