Analgesic Response to Opioid Analgesics in Buprenorphine-Maintained Individuals

Study Overview
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Brief Summary
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The aim of this study is to examine the effects of opioid analgesics on acute pain in participants maintained on buprenorphine+naloxone (Suboxone) for opioid use disorders. Seven medication conditions will be tested in a cold pressor test (CPT) paradigm.

Detailed Description
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Study design is a single-blind examination of the analgesic effects of a single dose of seven test medications provided in an experimental pain paradigm using a cold pressor test (CPT). Test medication conditions include buprenorphine, morphine, hydromorphone, hydrocodone, oxycodone, and two placebo conditions to match test medication formulations (oral tablet, sublingual tablet). Each medication condition will be tested on separate days (seven total days, completing within 12 weeks), with random assignment to order of study medications. After screening, eligible participants will be scheduled for 7 days of testing with test days at least 3 days apart to provide a sufficient medication wash-out period. Pain testing will utilize cold pressor tests (CPT), in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance. Participants will be given a practice trial to provide familiarity with the test and reduce test anxiety. Two CPTs will occur on each test day, and pre- and post-CPT assessments will be administered. Blood samples will be taken on each test day to measure blood levels of buprenorphine. Daily procedures include: (1) A baseline CPT (BL-CPT), (2) Administration of the test medication (active drug or placebo), (3) CPT administered at the time of maximum drug effect (Tmax-CPT) specific to medication (range 30-120 minutes), (4) Pupillometry conducted at baseline (before BL-CPT), and at time of maximum drug effect (before Tmax-CPT). Each participant will be discharged after clinical determination of the participant's safety and well-being. Testing will continue until twelve trials of each medication condition are completed.

Official Title
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Analgesic Response to Opioid Analgesics in Buprenorphine-Maintained Individuals

Conditions
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Analgesic Response

Intervention / Treatment
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* Drug: morphine sulfate
* Drug: hydrocodone
* Drug: hydromorphone HCI
* Drug: oxycodone
* Drug: buprenorphine
* Drug: oral tablet placebo
* Drug: sublingual tablet placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, in good general health 20-50 years old Fluent in English Maintained on buprenorphine for at least 3 months Able to complete testing/assessments for 7 test days within 12 weeks Approved for participation by buprenorphine-prescribing physician Exclusion Criteria: Known hypersensitivity to any of the test opioids Urine test positive for opioids (other than buprenorphine) or other illicit substances Current use of any additional opioid or analgesic medication (other than buprenorphine), medical marijuana, MAOI, tricyclic antidepressant, duloxetine, gabapentin, pregabalin, or other medication considered unsafe or having potential to influence pain perception as determined by study physician. Presence of acute pain condition or planned surgery during the study period Unstable vital signs as determined by the study physician. Current pattern of alcohol, benzodiazepine, or other sedative hypnotic use, as determined by the study medical clinician, which would preclude safe participation in the study; Pending legal action or other situation that might prevent remaining in the area for the duration of the study Current medical or psychiatric condition that could detract from study objectives, place the participant at risk, or interfere with treatment goals

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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

Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: morphine sulfate<br>30mg, single dose, | Drug: oral tablet placebo<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: single dose;|
| Experimental: hydrocodone<br>10mg single dose | Drug: oral tablet placebo<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: single dose;|
| Experimental: hydromorphone HCI<br>4mg single dose | Drug: oral tablet placebo<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: single dose;|
| Experimental: oxycodone<br>10 mg single dose | Drug: oral tablet placebo<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: single dose;|
| Experimental: buprenorphine<br>4 mg single dose | Drug: sublingual tablet placebo<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: single dose;|
| Placebo Comparator: oral tablet placebo<br>single dose | Drug: morphine sulfate<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: 30 mg, single dose;Drug: hydrocodone<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: 10mg single dose;Drug: hydromorphone HCI<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: 4 mg single dose;Drug: oxycodone<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: 10 mg single dose;|
| Placebo Comparator: sublingual tablet placebo<br>single dose | Drug: buprenorphine<br>* Participants will receive randomly assigned order of study drug (opioid) and then have 7 days of testing with test days at least 3 days apart. Pain testing will utilize cold pressor test, in which the participant submerges his arm and hand in a bath of ice cold water to determine pain threshold and tolerance.<br>* Other names: 4 mg single dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain detection | Pain detection is defined as the number of seconds it takes for the participant to feel pain. | 7 testing sessions over 12 weeks | 
| Pain tolerance | Pain tolerance is defined as the number of seconds it takes before the participant removes his hand from the ice water. | 7 testing sessions over 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pupillometry results | Examine pupillometry results in the context of administered opioid medications and associated cold pressor tests. | 7 testing sessions over 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, cold presser test, buprenorphine, opioids