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

April 6, 2026 updated by: William Ondo, MD
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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline (Predose) in Mean International Restless Legs Syndrome (IRLS) Rating Scale at End of Intervention Period
Time Frame: Baseline (Pre-intervention), and at 5 weeks
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)
Time Frame: Baseline (Pre-intervention), and at 5 weeks

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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean 24 Hour Restless Legs Syndrome (RLS) Diary at End of Intervention
Time Frame: at end of intervention Ecopipam, at end of intervention Placebo
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
Time Frame: At end of intervention Ecopipam, at end of intervention Placebo
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Mean From Baseline Epworth Sleep Scale (ESS) at the End of the Intervention
Time Frame: Baseline (Pre-intervention), and at Week 5
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
Time Frame: Baseline (Pre-intervention), and at Week 5
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
William Ondo, MD

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Restless Legs Syndrome Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: William G. Ondo, MD, The Methodist Hospital Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 18, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 28, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 28, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 17, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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