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

Sleep Disorder Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04759703
• Other study ID #: 2020P002928
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 24, 2022
• Est. completion date: June 1, 2025

Study information

• Verified date: March 2024
• Source: Massachusetts General Hospital
• Contact: Benjamin W Wipper
• Phone: 617-643-6026
• Email: bwipper[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Opioid Withdrawal
• Opioid-Related Disorders
• Opioid-use Disorder
• Psychomotor Agitation
• Restless Legs Syndrome
• Sleep Disorder
• Sleep Wake Disorders
• Substance Withdrawal Syndrome

Intervention

Drug:
• Pramipexole
0.25 mg pramipexole tablets
• Placebo
Matching placebo tablets

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Gavin Foundation Clinical Stabilization Services	Quincy	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

Hening 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. — View Citation

Walters 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline International Restless Legs Syndrome Study Group Scale (IRLS) at 2 weeks	A validated tool to measure restless legs syndrome severity, on a scale of 0-40, with a higher score representing greater restless legs syndrome severity	2 weeks
Secondary	Change from Baseline Subjective Opiate Withdrawal Scale (SOWS) at 2 weeks	The Subjective Opiate Withdrawal Scale (SOWS) is a 16-item self-administered instrument. One of the items queries for presence of 'restlessness'.	2 weeks