Buprenorphine Plus Baclofen to Increase Analgesia in Healthy Volunteers

To determine if baclofen will enhance buprenorphine analgesia for acute pain in healthy volunteers.

Study Overview

• Status: Active, not recruiting
• Conditions: Analgesia; Acute Pain
• Intervention / Treatment: Drug: Placebos; Drug: Baclofen 5 mg; Drug: Baclofen 10mg

Detailed Description

Abuse of opioids is a significant and growing problem in the United States. In the past two decades, opioid prescriptions have quadrupled while the age of heroin initiation has decreased, suggesting that more individuals are using opioids and transitioning to heroin and potent synthetic opioids than in the past. Further, fatal opioid overdose is now the leading cause of accidental death and is the 5th highest overall cause of mortality in the US. Engaging opioid users in opioid agonist treatments has been shown to lower rates of criminal behavior, lower rates of non-opioid drug use, and increase retention in drug treatment programs, while decreasing mortality and new HIV and hepatitis infections. However, a recent study noted that 68% of patients prescribed buprenorphine had poor medication adherence, which was associated with illicit opioid use. A Cochrane review concluded that buprenorphine was less effective at retaining patients in treatment relative to methadone. One reason for lower treatment retention may be the high comorbidity of opioid use disorder and chronic pain and/or opioid-induced hyperalgesia. Buprenorphine, as a partial mu agonist, provides lower analgesia but an improved safety profile relative to full agonists like methadone. Thus, enhancing the analgesic properties of buprenorphine will provide a safer alternative for opioid use disorder patients with chronic pain/hyperalgesia.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Karen L Cropsey, Psy.D.; Phone Number: 2059754204; Email: kcropsey@uab.edu
• Study Contact Backup: Name: Keith Chichester, B.A.; Phone Number: 2059757809; Email: krc80@uab.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • University of Alabama, Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 years or older
• general good health
• English speaking

Exclusion Criteria:

• Pregnant or nursing
• Opioid use disorder or any substance use disorder other than nicotine
• Prescribed agonist treatment for opioid dependence or prescribed opioids for a medical condition
• Prescribed naltrexone
• Known sensitivity to buprenorphine, naloxone, or baclofen
• Acute or chronic pain condition
• Trouble breathing or a pulmonary condition
• Prescribed benzodiazepines or daily use of benzodiazepines
• Positive drug screen (positive cannabis result allowed)
• Cognitive impairment or psychiatric disorder requiring treatment
• Uncontrolled hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants randomized to this arm will receive Placebo.	Drug: Placebos; Participants will receive placebo in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.
Experimental: Baclofen 5mg; Participants randomized to this arm will receive 5 mg of Baclofen.	Drug: Baclofen 5 mg; Participants will receive 5mg of baclofen in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.
Experimental: Baclofen 10mg; Participants randomized to this arm will receive 10 mg of Baclofen.	Drug: Baclofen 10mg; Participants will receive 10mg of baclofen in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Threshold	Pain threshold refers to the intensity at which a stimulus is first perceived as painful. Heat stimuli will be delivered using a computer-controlled thermal stimulation system with a 30 millimeter X 30 millimeter probe. From a baseline of 32 degrees Celsius, the probe temperature will increase at a rate of .5 degrees Celsius/second until the participant responds by pressing a button on a handheld device. For heat pain threshold, participants will be instructed to press the button when the sensation "first becomes painful" Pain rating scores will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain.	Baseline
Pain Threshold	Pain threshold refers to the intensity at which a stimulus is first perceived as painful. Heat stimuli will be delivered using a computer-controlled thermal stimulation system with a 30 millimeter X 30 millimeter probe. From a baseline of 32 degrees Celsius, the probe temperature will increase at a rate of .5 degrees Celsius/second until the participant responds by pressing a button on a handheld device. For heat pain threshold, participants will be instructed to press the button when the sensation "first becomes painful" Pain rating scores will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain.	Baseline through one week
Pain tolerance	Pain tolerance refers to the maximum amount of pain produced by a stimulus that a person is able/willing to tolerate. Heat stimuli will again be delivered using the computer-controlled thermal stimulation system. From a baseline of 32 degrees Celsius, the probe temperature will increase at a rate of .5 degrees Celsius/second until the participant responds by pressing a button on a handheld device. For heat pain tolerance, participants will be instructed to press the button when they are "no longer willing to tolerate" the painful sensation. Pain rating scores will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain.	Baseline
Pain tolerance	Pain tolerance refers to the maximum amount of pain produced by a stimulus that a person is able/willing to tolerate. Heat stimuli will again be delivered using the computer-controlled thermal stimulation system. From a baseline of 32 degrees Celsius, the probe temperature will increase at a rate of .5 degrees Celsius/second until the participant responds by pressing a button on a handheld device. For heat pain tolerance, participants will be instructed to press the button when they are "no longer willing to tolerate" the painful sensation. Pain rating scores will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain.	Baseline through one week
Temporal summation of pain	Temporal summation of pain refers to a form of endogenous pain facilitation characterized by the perception of increased pain despite constant or even reduced peripheral afferent input. Temporal summation is presumed to be the psychophysical manifestation of wind-up. Wind-up is a phenomenon where repetitive stimulation of C primary afferents at rates greater than 0.3 Hertz produces a slowly increasing response of second-order neurons in the spinal cord. Pain rating scores will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain.	Baseline
Temporal summation of pain	Temporal summation of pain refers to a form of endogenous pain facilitation characterized by the perception of increased pain despite constant or even reduced peripheral afferent input. Temporal summation is presumed to be the psychophysical manifestation of wind-up. Wind-up is a phenomenon where repetitive stimulation of C primary afferents at rates greater than 0.3 Hertz produces a slowly increasing response of second-order neurons in the spinal cord. Pain rating scores will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain.	Baseline through one week
Conditioned pain modulation	A routinely used quantitative sensory testing protocol for the measurement of endogenous pain inhibition is conditioned pain modulation, which refers to the reduction in pain from one stimulus (the test stimulus) produced by the application of a second pain stimulus at a remote body site (the conditioning stimulus). Conditioned pain modulation is believed to reflect the perceptual manifestation of diffuse noxious inhibitory controls, whereby ascending projections from one noxious stimulus activate supraspinal structures that trigger descending inhibitory projections to the dorsal horn. Pain rating scores will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain.	Baseline
Conditioned pain modulation	A routinely used quantitative sensory testing protocol for the measurement of endogenous pain inhibition is conditioned pain modulation, which refers to the reduction in pain from one stimulus (the test stimulus) produced by the application of a second pain stimulus at a remote body site (the conditioning stimulus). Conditioned pain modulation is believed to reflect the perceptual manifestation of diffuse noxious inhibitory controls, whereby ascending projections from one noxious stimulus activate supraspinal structures that trigger descending inhibitory projections to the dorsal horn. Pain rating scores will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain.	Baseline through one week
Suprathreshold pain response	Ratings of pain in response to discrete stimuli with intensities above the pain threshold detection/ patients provide an intensity rating using any number of a 0-100 scale whereby 0=no pain and 100= the most intense pain imaginable	Baseline
Suprathreshold pain response	Ratings of pain in response to discrete stimuli with intensities above the pain threshold detection/ patients provide an intensity rating using any number of a 0-100 scale whereby 0=no pain and 100= the most intense pain imaginable	Baseline through one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Symptom Checklist	Lists True-False questions measuring opioid effects.	One to seven days post baseline
McGill Pain Questionnaire-Short Form	15 descriptors (11 sensory; 4 affective) using an intensity scaled ranging from 0-3 on pain. 0 being the least amount of pain and 3 being the most amount of pain.	One to seven days post baseline
26-item Visual Analog Scale (VAS)	Measures subjective and physiological effects of a medication using mood states as well as questions about the dose of medication.	One to seven days post baseline
Drug Effects Questionnaire-5	Assesses drug effects and uses VAS ratings from "Not at all" to "Very much."	One to seven days post baseline
26-item Visual Analog Scale ("Subjective drug effects")	This 26-item VAS measures subjective and physiological effects of a medication using mood states as well as questions about the dose of medication.	One to seven days post baseline

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Karen L Cropsey, Psy.D., University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: December 18, 2019
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; GABA Agents; Neuromuscular Agents; Muscle Relaxants, Central; GABA Agonists; GABA-B Receptor Agonists; Baclofen
• Other Study ID Numbers: 300004505

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes