Opioid-use Disorder, Opioid Withdrawal, Restless Legs Syndrome, Sleep Disorder
Conditions
Keywords
Pramipexole
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.
Interventions
DRUGPramipexole
0.25 mg pramipexole tablets
DRUGPlacebo
Matching placebo tablets
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
After screening, 18 of the 93 patients were found ineligible and 35 withdrew or failed. 40 completed post randomization baseline data.
Participants by arm
| Arm | Count |
|---|---|
| Pramipexole 0.25 mg pramipexole tablets | 20 |
| Placebo Matching placebo tablets | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 9 |
Baseline characteristics
| Characteristic | Pramipexole | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 39.1 Years STANDARD_DEVIATION 9.6 | 37.3 Years STANDARD_DEVIATION 8.2 | 35.2 Years STANDARD_DEVIATION 5.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 36 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| International Restless Legs Syndrome Study Group Rating Scale (IRLS) | 14.94 scores on a scale STANDARD_DEVIATION 1.99 | 14.85 scores on a scale STANDARD_DEVIATION 1.92 | 14.71 scores on a scale STANDARD_DEVIATION 1.89 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 32 Participants | 17 Participants |
| Region of Enrollment United States | 20 Participants | 40 Participants | 20 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Male | 13 Participants | 30 Participants | 17 Participants |
| Subjective Opiate Withdrawal Scale (SOWS) | 21.18 scores on a scale STANDARD_DEVIATION 10 | 23.93 scores on a scale STANDARD_DEVIATION 10.52 | 26.40 scores on a scale STANDARD_DEVIATION 10.61 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 15 / 20 | 8 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
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
Time frame: baseline and 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole | Change From Baseline International RLS Severity Score (IRLS) at 2 Weeks | -7.04 scores on a scale | Standard Deviation 3.44 |
| Placebo | Change From Baseline International RLS Severity Score (IRLS) at 2 Weeks | -9.15 scores on a scale | Standard Deviation 6.56 |
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)
Time frame: baseline and 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole | Change From Baseline Subjective Opiate Withdrawal Scale (SOWS) at 2 Weeks | -11.60 scores on a scale | Standard Deviation 11.88 |
| Placebo | Change From Baseline Subjective Opiate Withdrawal Scale (SOWS) at 2 Weeks | -18.28 scores on a scale | Standard Deviation 13.41 |