Treatment of Restless Leg Syndrome (RLS) Augmentation With Ecopipam, a D1 Specific Antagonist (RLS-Ecopipam)

This is an exploratory, double blinded cross-over study of the D1 antagonist ecopipam treat patients currently having dopamine agonist induced augmentation in restless legs syndrome. Each arm is 6 weeks composed of an unforced titration up to 100mg/day separated by a 2-week wash-out period. Efficacy points will include the IRLS, augmentation scales, sleep scales, clinical impressions and fatigue/mood scales.

Study Overview

• Status: Completed
• Conditions: Restless Legs Syndrome; Augmentation
• Intervention / Treatment: Drug: Placebo; Drug: Ecopipam

Detailed Description

This is a double-blind, exploratory proof of concept, cross-over trial of the D1 antagonist ecopipam for subjects with augmented Restless legs syndrome (RLS). Investigators will recruit 10 subjects taking dopamine agonists for RLS who are currently experiencing augmentation. The goal is to have 8 completers. There is no power analysis as this is an exploratory study and there is no previous data on treatment of augmentation. "Meaningful improvement" is not even established. A safety analysis will be done after 5 subjects have been enrolled. Duration of study and is based mostly on contracted drug availability for this pilot study.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provide consent to participate in the study
• Individuals of either sex, 21-80 years of age
• Clinically defined Restless Leg Syndrome, and problematic augmentation currently on monotherapy with dopaminergic treatment.

Exclusion Criteria:

• Current use of Opioid medications
• Clinical relevant depression or other medical problems that in the opinion of the investigator would not allow for safe completion of the protocol.
• Suicidal ideation
• History of epilepsy
• Current MAO inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study period 1; Ecopipam or matching placebo 25 mg by mouth for 7 days (week 1), followed by; Ecopipam or matching placebo 50 mg by mouth for 7 days (week 2), followed by; Ecopipam or matching placebo 100 mg by mouth for 23 days (weeks 3).	Drug: Placebo; matching placebo; Drug: Ecopipam; oral drug in subjection currently experiencing dopamine agonist induced augmentation; Other Names: PSYRX101
Experimental: Study period 2; Matching placebo or ecopipam 25 mg by mouth for 7 days (week 7), followed by; Matching placebo or ecopipam 50 mg by mouth for 7 days (week 8), followed by; Matching placebo or ecopipam 100 mg by mouth for 23 days (week 9).	Drug: Placebo; matching placebo; Drug: Ecopipam; oral drug in subjection currently experiencing dopamine agonist induced augmentation; Other Names: PSYRX101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (Predose) in Mean International Restless Legs Syndrome (IRLS) Rating Scale at End of Intervention Period	IRLS scale is a patient-administered test that measures the severity of restless legs syndrome symptoms. The IRLS scale consists of 10 questions rated from 0 to 4. The total score on symptom severity range from 0 (none) to 40 (worst).	Baseline (Pre-intervention), and at 5 weeks
Change From Baseline in Mean Body Part Affected by RLS Symptoms Using Augmentation Severity Rating Scale (ASRS)	ASRS scale has three items and probes symptoms over the past week. The first item asks the time at which symptoms began in the last week. The second item probes how quickly symptoms begin when sitting at various times of the day during the past week, and the third item probes which body parts were involved in the past week. Each item has a total of 8 points for a 24-point total scale. 0 is no augmentation and 24 is the most severe augmentation. In the third item, participants are asked to shade in the figure the portions of his/her body affected by RLS symptoms for a total of 8 points. The higher the score the worse the outcome	Baseline (Pre-intervention), and at 5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 24 Hour Restless Legs Syndrome (RLS) Diary at End of Intervention	Patient reported diary of RLS symptoms 72 hours prior to clinic visit. Participants were asked to record the number of hours each day they were bothered by RLS symptoms and when symptoms were present but not bothersome. The range can be 0 (no symptoms) to 72 (uniterupted symptoms)	at end of intervention Ecopipam, at end of intervention Placebo
Number of Participants With Effect on the Clinical Global Impression Scale at the End of the Intervention	A Modified clinician-administered scale used to evaluate the effect of an intervention on participant symptoms. Responses range from None/worse, mild, Marked or very marked.	At end of intervention Ecopipam, at end of intervention Placebo

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean From Baseline Epworth Sleep Scale (ESS) at the End of the Intervention	The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.	Baseline (Pre-intervention), and at Week 5
Change in Mean Score From Baseline Montreal Cognitive Assessment (MoCA) at End of Intervention	The Montreal Cognitive Assessment (MoCA) was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Score range from 0 - 30 with lower scores reflecting worse outcomes.	Baseline (Pre-intervention), and at Week 5

Collaborators and Investigators

• Sponsor: William Ondo, MD
• Collaborators: Restless Legs Syndrome Foundation
• Investigators: Principal Investigator: William G. Ondo, MD, The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2017
• Primary Completion (Actual): September 28, 2018
• Study Completion (Actual): November 28, 2018

Study Registration Dates

• First Submitted: April 21, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Parasomnias; Restless Legs Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; ecopipam
• Other Study ID Numbers: Pro#00016705

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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