DISCO-RLS: DIalysis Symptom COntrol-Restless Legs Syndrome Trial

Sponsor

Population Health Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT03806530

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

26.7

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease Restless Legs Syndrome	Drug: Gabapentin Drug: Ropinirole Drug: Placebo Gabapentin Drug: Placebo Ropinirole	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

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).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

Official Title:

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

Actual Study Start Date :

May 1, 2019

Anticipated Primary Completion Date :

Sep 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

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 Gabapentin Placebo capsule Other Names: Placebo Drug: Placebo Ropinirole Placebo capsule Other Names: Placebo

Outcome Measures

Primary Outcome Measures

International Restless Legs Syndrome Study Group Rating Scale (IRLS) [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.

Secondary Outcome Measures

Restless Legs Syndrome-6 Scale (RLS-6) [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) [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) [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. [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nova Scotia Health Authority	Halifax	Nova Scotia	Canada	B3H 2Y9
2	St. Joseph's Hamilton Healthcare	Hamilton	Ontario	Canada	L8N 4A6
3	The Ottawa Hospital	Ottawa	Ontario	Canada	K1H 7W9