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

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.

Study Overview

• Status: Recruiting
• Conditions: Sleep Disorder; Restless Legs Syndrome; Opioid-use Disorder; Opioid Withdrawal
• Intervention / Treatment: Drug: Placebo; Drug: Pramipexole

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Benjamin W Wipper; Phone Number: 617-643-6026; Email: bwipper@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Not yet recruiting
      • Massachusetts General Hospital
      • Contact: Benjamin Wipper; Phone Number: 617-643-6026; Email: bwipper@mgh.harvard.edu
    • Quincy, Massachusetts, United States, 02170
      • Recruiting
      • Gavin Foundation Clinical Stabilization Services
      • Contact: Benjamin Wipper; Phone Number: 617-643-6026; Email: bwipper@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pramipexole; Medication arm; 0.25 or 0.5 mg of pramipexole	Drug: Pramipexole; 0.25 mg pramipexole tablets; Other Names: Mirapex
Placebo Comparator: Placebo; Placebo arm; 0.25 or 0.5 mg of placebo	Drug: Placebo; Matching placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: John W Winkelman, MD/PhD, Massachusetts General Hospital

Publications and helpful links

General 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 12, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pramipexole
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Chemically-Induced Disorders; Nervous System Diseases; Substance-Related Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Parasomnias; Narcotic-Related Disorders; Aberrant Motor Behavior in Dementia; Sleep Wake Disorders; Psychomotor Agitation; Restless Legs Syndrome; Opioid-Related Disorders; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole; Dexpramipexole
• Other Study ID Numbers: 2020P002928

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Per the NIH Policy on Data Sharing, the investigators will make the datasets available to other investigators following publication of the final study results.
• IPD Sharing Access Criteria: Requests must be in accordance with Mass General Brigham Policies and Harvard Medical School Guidelines.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No