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

Study Overview
=================
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.

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

Conditions
-----------------
Sleep Disorder, Restless Legs Syndrome, Opioid-use Disorder, Opioid Withdrawal

Intervention / Treatment
-----------------
* Drug: Pramipexole
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pramipexole<br>Medication arm; 0.25 or 0.5 mg of pramipexole | Drug: Pramipexole<br>* 0.25 mg pramipexole tablets<br>* Other names: Mirapex;|
| Placebo Comparator: Placebo<br>Placebo arm; 0.25 or 0.5 mg of placebo | Drug: Placebo<br>* Matching placebo tablets<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pramipexole