Discontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper

Study Overview
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Brief Summary
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Chronic opioid therapy for pain can be associated with significant risks, and a significant number of patients maintained on chronic opioids have continued pain and/or poor functioning. When patients need to or want to come off their opioid pain medications, there is little to guide physicians as to how to best help them do so, and it is not known how patients do after coming off opioid medications. The goals of this study are (1) to evaluate two medications in assisting patients in coming off their opioid pain medications and (2) determining outcomes after discontinuing opioids.

Official Title
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Discontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper

Conditions
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Chronic Pain, Opioid Pain Medication

Intervention / Treatment
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* Drug: Buprenorphine Initiation - Phase I
* Drug: Gabapentin + Buprenorphine - Phase II
* Drug: Placebo + Buprenorphine - Phase II
* Drug: Buprenorphine taper - Phase II


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 70 years of age Ability to speak and read in English Currently taking chronic opioid therapy for pain for at least 6 months On opioid dose of >60mg and <200mg oral morphine equivalents/day Voluntarily seeking opioid discontinuation Willing to attempt buprenorphine-assisted opioid discontinuation Willing to be randomized to gabapentin or placebo Have current physician who is actively prescribing opioids and who will be notified by the research team of the patient's entry into the study. Exclusion Criteria: Previous intolerance or allergy to buprenorphine or gabapentin Diagnostic & Statistical Manual -V criteria for substance use disorder currently or in the past (other than nicotine) Unstable medical or psychiatric condition that would preclude safe or meaningful participation (e.g. traumatic brain injury; severe mental illness; severe cardiac, renal, pulmonary, or liver disease) Current use of illicit drugs Maintenance on fentanyl or methadone Current treatment with gabapentin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase - Buprenorphine Initiation<br>In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol up to 16mg sublingually over an up to 8 hour induction window. Buprenorphine tolerability will be defined as pain level ≤ to baseline, withdrawal measures ≤ to baseline, and willingness to continue with taper. | Drug: Buprenorphine Initiation - Phase I<br>* In Phase I, we will determine buprenorphine tolerability using a one-day outpatient buprenorphine initiation protocol up to 16mg sublingually over an 8 hour induction window.<br>|
| Active Comparator: Phase II - Gabapentin + Buprenorphine<br>Subjects who tolerate sublingual buprenorphine initiation in Phase I will proceed to Phase II, which will involve randomization to gabapentin or placebo, 2 week stabilization period, and up to 8 week buprenorphine tapering period. Those randomized to gabapentin will receive up to 1600mg oral gabapentin (double blinded) divided three times daily, titrated over the 2 week stabilization period and continued during the buprenorphine tapering period. During the 2 week stabilization period, buprenorphine will also be titrated up to 24mg as needed/tolerated. | Drug: Gabapentin + Buprenorphine - Phase II<br>* Subjects who tolerate sublingual buprenorphine initiation in Phase I will proceed to Phase II, which will involve randomization to oral gabapentin or placebo, 2 week stabilization period, and up to 8 week buprenorphine tapering period. Those randomized to gabapentin will receive up to 1600mg gabapentin (double blinded) divided three times daily, titrated over the 2 week stabilization period and continued during the buprenorphine tapering period. During the 2 week stabilization period, buprenorphine will also be titrated up to 24mg as needed/tolerated.<br>|
| Placebo Comparator: Phase II - Placebo + Buprenorphine<br>Subjects who tolerate sublingual buprenorphine initiation in Phase I will proceed to Phase II, which will involve randomization to gabapentin or placebo, 2 week stabilization period, and up to 8 week buprenorphine tapering period. Those randomized to placebo will receive up to 1600mg oral placebo (double blinded) divided three times daily, titrated over the 2 week stabilization period and continued during the buprenorphine tapering period. During the 2 week stabilization period, buprenorphine will also be titrated up to 24mg as needed/tolerated. | Drug: Placebo + Buprenorphine - Phase II<br>* Subjects who tolerate sublingual buprenorphine initiation in Phase I will proceed to Phase II, which will involve randomization to oral gabapentin or placebo, 2 week stabilization period, and up to 8 week buprenorphine tapering period. Those randomized to placebo will receive up to 1600mg placebo (double blinded) divided three times daily, titrated over the 2 week stabilization period and continued during the buprenorphine tapering period. During the 2 week stabilization period, buprenorphine will also be titrated up to 24mg as needed/tolerated.<br>|
| Experimental: Phase II - Buprenorphine taper<br>After a 2 week stabilization period where sublingual buprenorphine is titrated up to 24 mg/day and oral gabapentin/placebo is titrated up to 1600mg/day, subjects will enter a buprenorphine tapering period lasting up to 8 weeks. The suggested buprenorphine taper will be determined by stabilizing dose, but able to be altered by prescriber or participant based on symptoms. | Drug: Buprenorphine taper - Phase II<br>* After a 2 week stabilization period where sublingual buprenorphine is titrated up to 24 mg/day and oral gabapentin/placebo is titrated up to 1600mg/day, subjects will enter a buprenorphine tapering period lasting up to 8 weeks. The suggested buprenorphine taper will be determined by stabilizing dose, but able to be altered by prescriber or participant based on symptoms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Tolerate Buprenorphine Initiation | For Phase I, the primary outcome measure is the percentage of patients who tolerate buprenorphine initiation within an 8-hour initiation period, as evidenced by a total score of 3 points when summing the following measures (1) moderate-good level of pain control (same or improved rating on a 0-10 visual analogue scale for pain) = 1 point, (2) mild to no withdrawal symptoms (≤10 on the Subjective Opioid Withdrawal Scale) = 1 point, and (3) willingness to continue to the stabilization and tapering phase of the study; yes = 1 point. | 8 hours post dose | 
| Number of Participants Who Achieve Opioid Cessation | For Phase II, the primary outcome measure will be number of participants opioid who achieve cessation 8 weeks after stabilization at Week 10, evidenced as a score of 3 points when summing the following measures: self-report of no opioid use = 1 point; prescription drug monitoring data showing no opioid prescriptions filled in past 30 days = 1 point; and confirmatory negative urine toxicology for a full panel of opioids = 1 point. | 8 weeks after stabilization at Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieve Opioid Cessation Post-taper: 1 Month | Opioid cessation post taper: 1 month with opioid cessation measured through self-report, prescription drug monitoring data, and confirmatory UDS for a full panel of opioids. | 1 month post-taper | 
| Pain Self-report: Pain Catastrophizing Scale - Baseline | The Self Reporting Pain Catastrophizing scale consists of 13 items scored from 0 to 4. The total possible score is 52. A higher score indicates more catastrophizing thoughts are present. A lower score indicates less catastrophizing thoughts. | Baseline | 
| Pain Laboratory Testing: Mechanical - Baseline | Mechanical (Pressure) Pain Threshold Assessment (PPTh): A digital anesthesiometer (IITC Life Sciences ElectroVonFrey) will be used to assess mechanical pain perception. Pain threshold to static mechanical stimuli will be determined by applying the rigid monofilament to the dorsum of each subject's right hand with increasing pressure (10 grams per second) until the participant indicates verbally that the pain threshold has been reached. | Baseline | 
| Mean Score of Current Opioid Measure (COMM) | COMM is a 17 item questionnaire that is used to examine concurrent misuse. The score range is from 0-28. A lower score represents participant showing less aberrant behaviors associates with misuse of option medications, and a higher score represents more aberrant behaviors associated with opioid medical misuse. | Baseline | 
| Mean Score of PROMIS Physical Function Short Form (PROMIS SF 10) - RAW SCORE PH | The Mean score of Physical Function on PROMIS short form. The global physical health score is a sum of responses to 4 questions. The range is from 4-20. A lower score represents lower physical function. The following questions will be asked: In general, how would you rate your physical health? (range is 1-5; 1 represents poor rating in health, 5 represents excellent rating of physical health) To what extent are you able to carry out your everyday physical activities such as walking, climbing stairs, carrying groceries, or moving a chair? (range is 1-5; 1 represents score of not at all, 5 represents score of completely) How would you rate your fatigue on average? (range is 1-5; 1 represents very severe fatigue, and 5 represents no fatigue) How would you rate your pain on average (range is 0-10; 0 represents no pain, 10 represents worst pain imaginable). The pain score is then recoded: 0, no pain = 5; 1, 2, or 3 = 4; 4, 5, or 6 =3; 7, 8, 9 =2;10 =1 | baseline | 
| Mean Score Pittsburgh Sleep Quality Index | The PSQI is a 19 item self-report questionnaire that assesses sleep quality over a 1-month time interval. The measure consists of 19 individual items, creating 7 components (time gone to bed, how long it takes to go to sleep, wake up time, hours slept, issues sleeping, total hours slept etc.) that produce one global score. Each item is weighted on a 0-3 interval scale. The global score is calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, A lower scale is indicative of better sleep quality and higher score represents poor sleep quality. | baseline | 
| Mean Score of Subjective Opioid Withdrawal Scale (SOWS) | The Subjective Opiate Withdrawal Scale (SOWS) consist of 16 symptoms rated in intensity by patients on a 5-point scale of intensity as follows: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely. The total score is a sum of item ratings, and ranges from 0 to 64. | baseline | 
| Number of Participants Who Achieved Opioid Cessation Post-taper - 3 Months | Opioid cessation is evidenced as a score of 3 points when summing the following measures: self-report of no opioid use = 1 point; prescription drug monitoring data showing no opioid prescriptions filled in past 30 days = 1 point; and confirmatory negative urine toxicology for a full panel of opioids = 1 point. | Post-taper - 3 months | 
| Number of Participants Who Achieved Opioid Cessation Post-taper - 6 Months | Opioid cessation is evidenced as a score of 3 points when summing the following measures: self-report of no opioid use = 1 point; prescription drug monitoring data showing no opioid prescriptions filled in past 30 days = 1 point; and confirmatory negative urine toxicology for a full panel of opioids = 1 point. | Post-taper - 6 months | 
| Number of Participants Who Achieved Opioid Cessation Post-taper - 12 Months | Opioid cessation is evidenced as a score of 3 points when summing the following measures: self-report of no opioid use = 1 point; prescription drug monitoring data showing no opioid prescriptions filled in past 30 days = 1 point; and confirmatory negative urine toxicology for a full panel of opioids = 1 point. | Post-taper - 12 months | 
| Pain Laboratory Measures - Descending Noxious Inhibitory Control (DNIC) - Average, Baseline | DNIC will be measured as the percent change in PPTh during the cold pressor tasks relative to baseline. A percent increase represents normal functioning of pain inhibitory processes. | Baseline |