Back to resultsDiscontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper
Primary Purpose
Chronic Pain, Opioid Pain Medication
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Buprenorphine Initiation - Phase I
Gabapentin + Buprenorphine - Phase II
Placebo + Buprenorphine - Phase II
Buprenorphine taper - Phase II
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Pain
Eligibility Criteria
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
Sites / Locations
- Medical University of South Carolina
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Placebo Comparator
Experimental
Arm Label
Phase - Buprenorphine Initiation
Phase II - Gabapentin + Buprenorphine
Phase II - Placebo + Buprenorphine
Phase II - Buprenorphine taper
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT02737826
First Posted
March 14, 2016
Last Updated
November 7, 2022
Sponsor
Medical University of South Carolina
1. Study Identification
Unique Protocol Identification Number
NCT02737826
Brief Title
Discontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper
Official Title
Discontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
May 2016 (Actual)
Primary Completion Date
December 9, 2019 (Actual)
Study Completion Date
January 13, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pain, Opioid Pain Medication
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase - Buprenorphine Initiation
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase II - Gabapentin + Buprenorphine
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Phase II - Placebo + Buprenorphine
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Phase II - Buprenorphine taper
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Buprenorphine Initiation - Phase I
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Gabapentin + Buprenorphine - Phase II
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo + Buprenorphine - Phase II
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Buprenorphine taper - Phase II
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Patients Who Tolerate Buprenorphine Initiation
Description
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.
Time Frame
8 hours post dose
Title
Number of Participants Who Achieve Opioid Cessation
Description
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.
Time Frame
8 weeks after stabilization at Week 10
Secondary Outcome Measure Information:
Title
Number of Participants Who Achieve Opioid Cessation Post-taper: 1 Month
Description
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.
Time Frame
1 month post-taper
Title
Pain Self-report: Pain Catastrophizing Scale - Baseline
Description
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.
Time Frame
Baseline
Title
Pain Laboratory Testing: Mechanical - Baseline
Description
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.
Time Frame
Baseline
Title
Mean Score of Current Opioid Measure (COMM)
Description
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.
Time Frame
Baseline
Title
Mean Score of PROMIS Physical Function Short Form (PROMIS SF 10) - RAW SCORE PH
Description
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
Time Frame
baseline
Title
Mean Score Pittsburgh Sleep Quality Index
Description
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.
Time Frame
baseline
Title
Mean Score of Subjective Opioid Withdrawal Scale (SOWS)
Description
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.
Time Frame
baseline
Title
Number of Participants Who Achieved Opioid Cessation Post-taper - 3 Months
Description
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.
Time Frame
Post-taper - 3 months
Title
Number of Participants Who Achieved Opioid Cessation Post-taper - 6 Months
Description
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.
Time Frame
Post-taper - 6 months
Title
Number of Participants Who Achieved Opioid Cessation Post-taper - 12 Months
Description
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.
Time Frame
Post-taper - 12 months
Title
Pain Laboratory Measures - Descending Noxious Inhibitory Control (DNIC) - Average, Baseline
Description
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.
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29424
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Discontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper
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