Treatment of Restless Legs Symptoms With Pramipexole to Improve the Outcomes of Protracted Opioid Withdrawal in OUD

Phase 2

Terminated

• Conditions: Opioid Withdrawal; Sleep Disorder; Restless Legs Syndrome; Opioid-use Disorder
• Interventions: Drug: Pramipexole; Drug: Placebo

• Registration Number: NCT04759703
• Lead Sponsor: Massachusetts General Hospital

Brief 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.

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 Timeline

• Study First Submitted: 2021-02-12
• Study First Submitted QC: 2021-02-16
• Study First Posted: 2021-02-18
• Study Start: 2022-01-24
• Primary Completion: 2024-05-24
• Study Completion: 2024-05-24
• Status Verified: 2025-09
• Results First Submitted: 2025-09-12
• Results First Submitted QC: 2025-09-18
• Last Update Submitted: 2025-09-18
• Results First Posted: 2025-09-22
• Last Update Posted: 2025-09-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

1. Men or women of any ethnic origin.
2. Written informed consent is obtained
3. Speaks and writes in English
4. A willingness and ability to comply with study procedures.
5. Age 18-75 years
6. 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
7. Diagnosis of RLS from the Hening Telephone Diagnostic Interview (HTDI) with subsequent confirmation by clinical interview conducted by a study physician
8. International Restless Legs Syndrome Severity Scale (IRLS) Symptoms subscale score of >15 for three consecutive days prior to randomization

Exclusion Criteria

1. Receiving opioid-agonist medications at transfer to the CSS
2. Pregnant
3. Participants with active or unstable major psychiatric disorder other than OUD, who, in the investigators' judgment, require further treatment
4. Use of dopaminergic agonists or antagonists within the last 30 days
5. Alcohol use disorder within the last 30 days
6. History of being treated for RLS, specifically with dopamine agonist medications
7. Methamphetamine or benzodiazepine dependence in the last 30 days
8. 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
9. Medical instability considered to interfere with study procedures
10. Stage 3, 4, or 5 renal insufficiency
11. Participation in this study on a previous admission to the CSS

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pramipexole	Pramipexole	Medication arm; 0.25 of pramipexole
Placebo	Placebo	Placebo arm; 0.25 mg of placebo

Primary Outcome Measures

Name	Time	Method
Change From Baseline International RLS Severity Score (IRLS) at 2 Weeks	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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline Subjective Opiate Withdrawal Scale (SOWS) at 2 Weeks	baseline and 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)

Trial Locations

Locations (2)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Gavin Foundation Clinical Stabilization Services; 🇺🇸 Quincy, Massachusetts, United States