Sleep DisorderPhase 2/3NCT04759703
Treatment of Restless Legs Symptoms With Pramipexole to Improve the Outcomes of Protracted Opioid Withdrawal in OUD
A Phase 2/3 study testing Pramipexole in people with Sleep Disorder and Restless Legs Syndrome, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
The investigators propose to test the use of pramipexole in patients being treated for Opioid Use Disorder to test its ability to reduce symptoms of both Restless Legs Syndrome and protracted opioid withdrawal and thereby promote initiation, engagement, and retention in treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Sleep Disorder, Restless Legs Syndrome, Opioid-use Disorder
- What is being tested?
- Pramipexole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Jan 2022to 24 May 2024
- Phase
- Phase 2/3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women of any ethnic origin.
- Written informed consent is obtained
- Speaks and writes in English
- A willingness and ability to comply with study procedures.
- Age 18-75 years
- Patients with diagnosed OUD who have undergone primary detoxification for their OUD in the Gavin Acute Treatment Service (ATS), have been transferred to the Gavin Clinical Stabilization Service (CSS), and have some persistent opioid withdrawal as indicated by a Subjective Opiate Withdrawal Scale (SOWS) >1 on Day 1
- Diagnosis of RLS from the Hening Telephone Diagnostic Interview (HTDI) with subsequent confirmation by clinical interview conducted by a study physician
- International Restless Legs Syndrome Severity Scale (IRLS) Symptoms subscale score of >15 for three consecutive days prior to randomization
Who cannot join
- Receiving opioid-agonist medications at transfer to the CSS
- Pregnant
- Participants with active or unstable major psychiatric disorder other than OUD, who, in the investigators' judgment, require further treatment
- Use of dopaminergic agonists or antagonists within the last 30 days
- Alcohol use disorder within the last 30 days
- History of being treated for RLS, specifically with dopamine agonist medications
Show all 11Show fewer
- Methamphetamine or benzodiazepine dependence in the last 30 days
- Neurological disorder or cardiovascular disease raising safety concerns about use of pramipexole and/or judged to interfere with ability to assess efficacy of the treatment
- Medical instability considered to interfere with study procedures
- Stage 3, 4, or 5 renal insufficiency
- Participation in this study on a previous admission to the CSS
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Gavin Foundation Clinical Stabilization Services
Quincy, Massachusetts, 02170
About this study
Official title: Treatment of Restless Legs Symptoms With Pramipexole to Improve the Outcomes of Protracted Opioid Withdrawal in OUD: A Pilot Double-blind, Randomized Clinical Trial
The investigators propose to test the use of pramipexole in patients being treated for Opioid Use Disorder to test its ability to reduce symptoms of both Restless Legs Syndrome and protracted opioid withdrawal and thereby promote initiation, engagement, and retention in treatment.
Read the detailed description
This is a parallel, two-arm, double-blind, randomized placebo-controlled 2-week trial investigating the effects of pramipexole 0.25-0.5 mg on Restless Legs Syndrome (RLS) symptoms in patients suffering from opioid withdrawal. The investigators hypothesize that pramipexole is an effective treatment for RLS symptoms in Opioid Use Disorder (OUD) patients during post-detox clinical stabilization. Further, the investigators hypothesize that treatment of RLS in this context will also improve overall symptoms of opioid withdrawal.
RLS is a sensory-motor neurological disorder characterized by an irresistible urge to move the legs. The investigators have recently confirmed anecdotal reports that RLS is common among patients with OUD experiencing opioid withdrawal. Dopamine agonists such as pramipexole are efficacious and first-line FDA-approved treatments in low doses for RLS.
Recruitment and enrollment will occur at the Gavin Foundation Clinical Stabilization Services (CSS) in Quincy, Massachusetts. Eligible patients will be randomized to two weeks of pramipexole or placebo after an initial 3-day screening period and will be asked to complete 5 remote study visits over video or phone. Participants will be asked to complete sleep diaries and questionnaires at various points throughout the study.
- Being tested
- Pramipexole, Placebo
- Keywords
- Pramipexole
- Medical subject headings
- Sleep Wake Disorders, Restless Legs Syndrome, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PramipexoleDrug
Also called Mirapex
0.25 mg pramipexole tablets
PlaceboDrug
Matching placebo tablets
| Study group | Role | What they receive |
|---|---|---|
| Pramipexole | Experimental | Medication arm; 0.25 of pramipexole Receives: Drug: Pramipexole |
| Placebo | Placebo comparator | Placebo arm; 0.25 mg of placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline International RLS Severity Score (IRLS) at 2 Weeks
The International Restless Legs Syndrome Study Group Rating Scale (IRLS) is a 10-item patient-reported questionnaire designed to assess the severity of restless legs syndrome symptoms. Each item is scored from 0 (no symptoms) to 4 (very severe), for a total score range of 0 to 40, with higher scores indicating greater symptom severity. A negative change from baseline represents symptom improvement.
Very severe=31-40 points Severe=21-30 points Moderate=11-20 points Mild=1-10 points None=0 points
Change 2 weeks IRLS score minus baseline IRLS score
Measured: baseline and 2 weeks
Secondary outcomes (1)
Change From Baseline Subjective Opiate Withdrawal Scale (SOWS) at 2 Weeks
The Subjective Opiate Withdrawal Scale (SOWS) is a 16-item self-administered instrument.
Self-administered scale for grading opioid withdrawal symptoms. Scored from 0-64. Summed from 16 sub-scale questions rated by the patient from 0 to 4.
Mild Withdrawal = score of 1 - 10 Moderate withdrawal = 11 - 20 Severe withdrawal = 21 - 30+
Change in SOWS score (2 weeks minus baseline)
Measured: baseline and 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start24 Jan 2022
- Primary completion24 May 2024
- Study completion24 May 2024
Why it stopped: An interim analysis indicated that we would need to enroll more subjects than our initial enrollment target, in order to demonstrate a significant treatment effect. Due to these results, we have decided to terminate this protocol.
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sleep DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Winkelman, MD, PhD, Massachusetts General Hospital
- Investigators
- John W Winkelman, MD/PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04759703
- Sponsor's protocol ID
- 2020P002928
- Other IDs
- R21DA052861
- Status last verified
- Sep 2025
- First submitted
- 12 Feb 2021
- Last updated
- 22 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators will make data available on a public database. Outside investigators should submit their request in writing to the PI. A data-sharing agreement will be required. The request must be in accordance with Mass General Brigham (MGB) Policies and Harvard Medical School (HMS) Guidelines. Such datasets will not contain identifying information per the regulations outlined in HIPPA, and permission will be obtained from study participants to share their data with researchers outside MGB. Per standard MGB policies, the investigators will require a data-sharing agreement from any investigator or entity requesting the data; this agreement will include: (i) a commitment to using the data only for research purposes and not to identify any individual participant; (ii) a commitment to securing the data using appropriate computer technology; and (iii) a commitment to destroying or returning the data after analyses are completed.
Publications
Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987;13(3):293-308. doi: 10.3109/00952998709001515.
PubMed 3687892Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C; International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003 Mar;4(2):121-32. doi: 10.1016/s1389-9457(02)00258-7.
PubMed 14592342Hening WA, Allen RP, Washburn M, Lesage S, Earley CJ. Validation of the Hopkins telephone diagnostic interview for restless legs syndrome. Sleep Med. 2008 Mar;9(3):283-9. doi: 10.1016/j.sleep.2007.04.021. Epub 2007 Jul 17.
PubMed 17644424
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Restless Legs Symptoms With Pramipexole to Improve the Outcomes of Protracted Opioid Withdrawal in OUD: A Pilot Double-blind, Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04759703
- Acronym / sponsor ID
- 2020P002928
- Keywords
- Pramipexole
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: An interim analysis indicated that we would need to enroll more subjects than our initial enrollment target, in order to demonstrate a significant treatment effect. Due to these results, we have decided to terminate this protocol.
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 24 Jan 2022 (actual)
- Primary completion
- 24 May 2024 (actual)
- Study completion
- 24 May 2024 (actual)
- First posted
- 18 Feb 2021 (actual)
- Results
- Posted 22 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose to test the use of pramipexole in patients being treated for Opioid Use Disorder to test its ability to reduce symptoms of both Restless Legs Syndrome and protracted opioid withdrawal and thereby promote initiation, engagement, and retention in treatment.
Detailed description
This is a parallel, two-arm, double-blind, randomized placebo-controlled 2-week trial investigating the effects of pramipexole 0.25-0.5 mg on Restless Legs Syndrome (RLS) symptoms in patients suffering from opioid withdrawal. The investigators hypothesize that pramipexole is an effective treatment for RLS symptoms in Opioid Use Disorder (OUD) patients during post-detox clinical stabilization. Further, the investigators hypothesize that treatment of RLS in this context will also improve overall symptoms of opioid withdrawal.
RLS is a sensory-motor neurological disorder characterized by an irresistible urge to move the legs. The investigators have recently confirmed anecdotal reports that RLS is common among patients with OUD experiencing opioid withdrawal. Dopamine agonists such as pramipexole are efficacious and first-line FDA-approved treatments in low doses for RLS.
Recruitment and enrollment will occur at the Gavin Foundation Clinical Stabilization Services (CSS) in Quincy, Massachusetts. Eligible patients will be randomized to two weeks of pramipexole or placebo after an initial 3-day screening period and will be asked to complete 5 remote study visits over video or phone. Participants will be asked to complete sleep diaries and questionnaires at various points throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pramipexole | Experimental | Drug: PramipexoleMedication arm; 0.25 of pramipexole |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo arm; 0.25 mg of placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men or women of any ethnic origin.
- Written informed consent is obtained
- Speaks and writes in English
- A willingness and ability to comply with study procedures.
- Age 18-75 years
Key exclusion criteria (11 listed)
- Receiving opioid-agonist medications at transfer to the CSS
- Pregnant
- Participants with active or unstable major psychiatric disorder other than OUD, who, in the investigators' judgment, require further treatment
- Use of dopaminergic agonists or antagonists within the last 30 days
- Alcohol use disorder within the last 30 days
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 |
|---|---|---|
| PramipexoleAlso: Mirapex0.25 mg pramipexole tablets | Drug | Pramipexole |
| PlaceboMatching placebo tablets | Drug | Placebo |
Primary outcome
Change From Baseline International RLS Severity Score (IRLS) at 2 Weeks
Time frame: baseline and 2 weeks
The International Restless Legs Syndrome Study Group Rating Scale (IRLS) is a 10-item patient-reported questionnaire designed to assess the severity of restless legs syndrome symptoms. Each item is scored from 0 (no symptoms) to 4 (very severe), for a total score range of 0 to 40, with higher scores indicating greater symptom severity. A negative change from baseline represents symptom improvement. Very severe=31-40 points Severe=21-30 points Moderate=11-20 points Mild=1-10 points None=0 points Change 2 weeks IRLS score minus baseline IRLS score
1 secondary outcome
Change From Baseline Subjective Opiate Withdrawal Scale (SOWS) at 2 Weeks
Time frame: baseline and 2 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3687892Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987;13(3):293-308. doi: 10.3109/00952998709001515.
- Background: PubMed 14592342Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C; International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med. 2003 Mar;4(2):121-32. doi: 10.1016/s1389-9457(02)00258-7.
- Background: PubMed 17644424Hening WA, Allen RP, Washburn M, Lesage S, Earley CJ. Validation of the Hopkins telephone diagnostic interview for restless legs syndrome. Sleep Med. 2008 Mar;9(3):283-9. doi: 10.1016/j.sleep.2007.04.021. Epub 2007 Jul 17.
- Individual participant dataSharing planned: Yes. The investigators will make data available on a public database. Outside investigators should submit their request in writing to the PI. A data-sharing agreement will be required. The request must be in accordance with Mass General Brigham (MGB) Policies and Harvard Medical School (HMS) Guidelines. Such datasets will not contain identifying information per the regulations outlined in HIPPA, and permission will be obtained from study participants to share their data with researchers outside MGB. Per standard MGB policies, the investigators will require a data-sharing agreement from any investigator or entity requesting the data; this agreement will include: (i) a commitment to using the data only for research purposes and not to identify any individual participant; (ii) a commitment to securing the data using appropriate computer technology; and (iii) a commitment to destroying or returning the data after analyses are completed.
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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.
John W Winkelman, MD/PhD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pramipexole in people with Sleep Disorder and Restless Legs Syndrome, run by Massachusetts General Hospital at 2 sites 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 8 inclusion and 11 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: stopped early, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 22 Sep 2025). 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 International RLS Severity Score (IRLS) at 2 Weeks (time frame: baseline and 2 weeks). 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 NCT04759703, which also lists 3 linked publications.
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 22 Sep 2025.