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| ID | Type | Description | Link |
|---|---|---|---|
| R21DA052861 | U.S. NIH Grant/Contract | View source |
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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.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pramipexole | Experimental | Medication arm; 0.25 of pramipexole |
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| Placebo | Placebo Comparator | Placebo arm; 0.25 mg of placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pramipexole | Drug | 0.25 mg pramipexole tablets |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | baseline and 2 weeks |
| 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. 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John W Winkelman, MD/PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Gavin Foundation Clinical Stabilization Services |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 3687892 | Background | 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. | |
| 14592342 | Background | 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. |
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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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Per the NIH Policy on Data Sharing, the investigators will make the datasets available to other investigators following publication of the final study results.
Requests must be in accordance with Mass General Brigham Policies and Harvard Medical School Guidelines.
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After screening, 18 of the 93 patients were found ineligible and 35 withdrew or failed. 40 completed post randomization baseline data.
Participants were recruited from the Gavin Foundation Clinical Stabilization Services in Quincy. A total of 175 patients were referred, 93 were screened, and 75 patients enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pramipexole | 0.25 mg pramipexole tablets |
| FG001 | Placebo | Matching placebo tablets |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 26, 2024 |
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| Placebo | Drug | Matching placebo tablets |
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| baseline and 2 weeks |
| Quincy |
| Massachusetts |
| 02170 |
| United States |
| 17644424 | Background | 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. |
| COMPLETED |
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| NOT COMPLETED |
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Of 75 enrolled, 35 participants Withdrew/Failed before baseline data collected
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| ID | Title | Description |
|---|---|---|
| BG000 | Pramipexole | 0.25 mg pramipexole tablets |
| BG001 | Placebo | Matching placebo tablets |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age in years at screening date | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | Participants |
| ||||||||||||||||
| Subjective Opiate Withdrawal Scale (SOWS) | Subjective Opiate Withdrawal Scale (SOWS) Self-administered scale for grading opioid withdrawal symptoms. Scored from 0-64. Summed from 16 sub-scale questions from 0 to 4. Mild Withdrawal = score of 1 - 10 Moderate withdrawal = 11 - 20 Severe withdrawal = 21 - 30+ | Mean | Standard Deviation | scores on a scale |
| ||||||||||||||
| International Restless Legs Syndrome Study Group Rating Scale (IRLS) | Subjective assessment of primary features of restless legs syndrome, intensity and frequency, associated sleep problems Scored form 0-40. Summed from 10 sub-scale questions rated by the patient from 0 to 4. Very severe=31-40 points Severe=21-30 points Moderate=11-20 points Mild=1-10 points None=0 points | Mean | Standard Deviation | scores on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. 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) | Posted | Mean | Standard Deviation | scores on a scale | baseline and 2 weeks |
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| Primary | 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 | Posted | Mean | Standard Deviation | scores on a scale | baseline and 2 weeks |
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From enrollment through study termination, up to 2 weeks after randomization
Adverse events were collected daily by systemic assessment during inpatient stay and study visits.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pramipexole | 0.25 mg pramipexole tablets | 0 | 20 | 0 | 20 | 15 | 20 |
| EG001 | Placebo | Matching placebo tablets | 0 | 20 | 0 | 20 | 8 | 20 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stomach cramps | Gastrointestinal disorders | Systematic Assessment | Self-reported, mild to moderate |
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| Constipation | Gastrointestinal disorders | Systematic Assessment | Self-reported, mild |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Headaches | Nervous system disorders | Systematic Assessment |
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| Worsened RLS | Nervous system disorders | Systematic Assessment |
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| Drowsiness | General disorders | Systematic Assessment |
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| Jumpiness | Nervous system disorders | Systematic Assessment |
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| Muscle twitches | Nervous system disorders | Systematic Assessment |
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| Dry Mouth | Gastrointestinal disorders | Systematic Assessment |
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| Vivid Dreams | Psychiatric disorders | Systematic Assessment |
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This study was terminated early and did not complete planned enrollment. There was a target enrollment of 160, but the study only got to 75 enrolled. Of those 75, only 40 received treatment (20 pramipexole, 20 placebo). Limited sample size limits reliability of analyses and adverse events may not be representative of the broader study population.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John W. Winkelman, MD, PhD | Massachusetts General Hospital | 6176436026 | JWWINKELMAN@MGH.HARVARD.EDU |
| Sep 11, 2025 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012893 | Sleep Wake Disorders |
| D012148 | Restless Legs Syndrome |
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001523 | Mental Disorders |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D020447 | Parasomnias |
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
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| ID | Term |
|---|---|
| D000077487 | Pramipexole |
| ID | Term |
|---|---|
| D052160 | Benzothiazoles |
| D013844 | Thiazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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