Restless Legs SyndromePhase 1/2RLS-EcopipamNCT03218969

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

A Phase 1/2 study testing Ecopipam in people with Restless Legs Syndrome and Augmentation, run by William Ondo, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Restless Legs Syndrome, Augmentation
What is being tested?: Ecopipam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 10 participants
Where: 1 siteUnited States
Study dates: 18 Sep 2017to 28 Nov 2018
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Houston Methodist Hospital
Houston, Texas, 77030

Other trials in United States

About this study

Read the 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.

Conditions: Restless Legs Syndrome, Augmentation
Being tested: Ecopipam, Placebo
Medical subject headings: Restless Legs Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EcopipamDrug
Also called PSYRX101
oral drug in subjection currently experiencing dopamine agonist induced augmentation
PlaceboDrug
matching placebo

Study groups in NCT03218969
Study group	Role	What they receive
Study period 1	Experimental	* 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). Receives: Drug: Ecopipam; Drug: Placebo
Study period 2	Experimental	* 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). Receives: Drug: Ecopipam; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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
Measured: Baseline (Pre-intervention), and at 5 weeks

Secondary outcomes (2)

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)
Measured: 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.
Measured: At end of intervention Ecopipam, at end of intervention Placebo

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Sep 201728 Nov 2018

First posted17 Jul 2017
Study start18 Sep 2017
Primary completion28 Sep 2018
Study completion28 Nov 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Restless Legs SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03218969
Sponsor's protocol ID: Pro#00016705
Acronym: RLS-Ecopipam
Status last verified: Apr 2026
First submitted: 21 Apr 2017
Last updated: 27 Apr 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Lemborexant vs Clonidine vs Sedatives to Treat Insomnia in Chronic Pain Patients
Chronic Insomnia, Chronic Pain
Not yet recruiting
Neuromodulation to Overcome Severe Restless Legs Syndrome
Restless Leg Syndrome (RLS), Spinal Cord Stimulation (SCS)
Not yet recruitingPhase 2
Tolerability and Efficacy of CBD Extract for RLS Treatment
Restless Leg Syndrome
Recruiting
Functional Connectivity of the Interoceptive Network in RLS
Restless Legs Syndrome
Not yet recruitingPhase 2
Intravenous Iron in the Management of Drug-resistant Restless Legs syndromeI
Restless Legs Syndrome (RLS)

All Restless Legs Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Treatment of Restless Leg Syndrome (RLS) Augmentation With Ecopipam, a D1 Specific Antagonist
ClinicalTrials.gov ID: NCT03218969
Acronym / sponsor ID: RLS-Ecopipam / Pro#00016705
Conditions: Restless Legs Syndrome, Augmentation
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: William Ondo, MDUniversity, hospital or other
Collaborators: Restless Legs Syndrome Foundation
Study start: 18 Sep 2017 (actual)
Primary completion: 28 Sep 2018 (actual)
Study completion: 28 Nov 2018 (actual)
First posted: 17 Jul 2017 (actual)
Results: Posted 27 Apr 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Study period 1	Experimental	Drug: Ecopipam, Drug: Placebo* 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).
Study period 2	Experimental	Drug: Ecopipam, Drug: Placebo* 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).

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EcopipamAlso: PSYRX101oral drug in subjection currently experiencing dopamine agonist induced augmentation	Drug	Study period 1, Study period 2
Placebomatching placebo	Drug	Study period 1, Study period 2

Primary outcome

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).
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

2 secondary outcomes

Mean 24 Hour Restless Legs Syndrome (RLS) Diary at End of Intervention
Time frame: 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

Results and safety

Results posted to the registry on 27 Apr 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ecopipam First, Then Placebo	5	4
Placebo First, Then Ecopipam	5	5

Primary outcome: 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. Mean (Standard Deviation). Unit: score on a scale

Measure	Ecopipam n = 10	Placebo n = 9
IRLS mean at Baseline (Pre-intervention))	20.6 (6.5)	21.6 (7.89)
IRLS mean at Week 5 (end of intervention)	16 (10.6)	18.8 (8.62)

Population analysed: All participants who received at least one dose of each intervention were included in the analysis

Primary outcome: 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. Mean (Standard Deviation). Unit: score on a scale

Measure	Ecopipam n = 10	Placebo n = 9
Mean affected body part at Baseline	3.1 (1.52)	2.44 (1.33)
Mean affected body part at week 5	2.9 (1.6)	2.33 (1.41)

Population analysed: All participants who received at least one dose of each intervention were included in the analysis.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 5 weeks for each interevention. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ecopipam	0 of 10 (0%)	6 of 10 (60%)	0 of 10
Placebo	1 of 9 (11.1%)	6 of 9 (66.7%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Undecided

Related trials for Restless Legs Syndrome

RecruitingObservational study
Lemborexant vs Clonidine vs Sedatives to Treat Insomnia in Chronic Pain Patients
Chronic Insomnia, Chronic Pain
Not yet recruiting
Neuromodulation to Overcome Severe Restless Legs Syndrome
Restless Leg Syndrome (RLS), Spinal Cord Stimulation (SCS)
Not yet recruitingPhase 2
Tolerability and Efficacy of CBD Extract for RLS Treatment
Restless Leg Syndrome
Recruiting
Functional Connectivity of the Interoceptive Network in RLS
Restless Legs Syndrome
Not yet recruitingPhase 2
Intravenous Iron in the Management of Drug-resistant Restless Legs syndromeI
Restless Legs Syndrome (RLS)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

William G. Ondo, MD principal investigator

The Methodist Hospital Research Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ecopipam in people with Restless Legs Syndrome and Augmentation, run by William Ondo, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03218969.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026.