Analgesic Response to Opioid Analgesics in Buprenorphine-Maintained Individuals

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.

Study Overview

• Status: Unknown
• Conditions: Analgesic Response
• Intervention / Treatment: Drug: oral tablet placebo; Drug: sublingual tablet placebo; Drug: morphine sulfate; Drug: hydrocodone; Drug: hydromorphone HCI; Drug: oxycodone; Drug: buprenorphine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • UCLA Integrated Substance Abuse Programs Outpatient Clinical Research Center
      • Contact: Maureen Hillhouse, PhD; Phone Number: 310-267-5308; Email: hillhous@ucla.edu
      • Contact: Jessica Jenkins, MS; Phone Number: 310-267-5318; Email: jenkinsj@ucla.edu
      • Principal Investigator: Walter Ling, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male, in good general health
2. 20-50 years old
3. Fluent in English
4. Maintained on buprenorphine for at least 3 months
5. Able to complete testing/assessments for 7 test days within 12 weeks
6. Approved for participation by buprenorphine-prescribing physician

Exclusion Criteria:

1. Known hypersensitivity to any of the test opioids
2. Urine test positive for opioids (other than buprenorphine) or other illicit substances
3. 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.
4. Presence of acute pain condition or planned surgery during the study period
5. Unstable vital signs as determined by the study physician.
6. 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;
7. Pending legal action or other situation that might prevent remaining in the area for the duration of the study
8. Current medical or psychiatric condition that could detract from study objectives, place the participant at risk, or interfere with treatment goals

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: morphine sulfate; 30mg, single dose,	Drug: oral tablet placebo; 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.; Other Names: single dose
Experimental: hydrocodone; 10mg single dose	Drug: oral tablet placebo; 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.; Other Names: single dose
Experimental: hydromorphone HCI; 4mg single dose	Drug: oral tablet placebo; 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.; Other Names: single dose
Experimental: oxycodone; 10 mg single dose	Drug: oral tablet placebo; 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.; Other Names: single dose
Experimental: buprenorphine; 4 mg single dose	Drug: sublingual tablet placebo; 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.; Other Names: single dose
Placebo Comparator: oral tablet placebo; single dose	Drug: morphine sulfate; 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.; Other Names: 30 mg, single dose; Drug: hydrocodone; 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.; Other Names: 10mg single dose; Drug: hydromorphone HCI; 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.; Other Names: 4 mg single dose; Drug: oxycodone; 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.; Other Names: 10 mg single dose
Placebo Comparator: sublingual tablet placebo; single dose	Drug: buprenorphine; 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.; Other Names: 4 mg single dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Indivior Inc.
• Investigators: Principal Investigator: Walter Ling, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: May 9, 2014
• First Posted (Estimate): May 13, 2014

Study Record Updates

• Last Update Posted (Estimate): May 13, 2014
• Last Update Submitted That Met QC Criteria: May 9, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: buprenorphine; pain; opioids; cold presser test
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Respiratory System Agents; Antitussive Agents; Buprenorphine; Morphine; Oxycodone; Hydromorphone; Hydrocodone
• Other Study ID Numbers: 13-001175