Buprenorphine Plus Baclofen to Increase Analgesia in Healthy Volunteers

NCT04251819 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 300004505
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Pain; Analgesia

Outcome Measures

Primary Outcomes (10)

• 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.

  1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

• 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.

  1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

• 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.

  1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

• 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 for the test stimulus and the conditioning stimulus will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain. The conditioned pain modulation score is the difference between the two pain rating scores.

  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 for the test stimulus and the conditioning stimulus will be reflected in scores of 0-100, 0 being the least amount of pain and 100 being the most amount of pain. The conditioned pain modulation score is the difference between the two pain rating scores.

  1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

• 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

  1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

Secondary Outcomes (4)

• Opioid Symptom Checklist

  30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

• 26-item Visual Analog Scale (VAS)

  30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

• Drug Effects Questionnaire-5

  30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

• 26-item Visual Analog Scale ("Subjective Drug Effects")

  30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants randomized to this arm will receive one dosage of Placebo as part of their second study appointment.

Drug: Placebos

Baclofen 5mg

EXPERIMENTAL

Participants randomized to this arm will receive one dosage of 5 mg of Baclofen as part of their second study appointment.

Drug: Baclofen 5 mg

Baclofen 10mg

EXPERIMENTAL

Participants randomized to this arm will receive one dosage of 10 mg of Baclofen as part of their second study appointment.

Drug: Baclofen 10mg

Interventions

Placebos DRUG

Participants will receive placebo in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.

Placebo

Baclofen 5 mg DRUG

Participants will receive 5mg of baclofen in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.

Baclofen 5mg

Baclofen 10mg DRUG

Participants will receive 10mg of baclofen in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.

Baclofen 10mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• general good health
• English speaking

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama, Birmingham

Birmingham, Alabama, 35209, United States

Location

MeSH Terms

Conditions

Acute Pain; Agnosia

Interventions

Baclofen

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Karen Cropsey
• Organization: UAB

kcropsey@uabmc.edu

2059754204

Study Officials

• Karen L Cropsey, Psy.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: Participants will be randomized to one of three interventions.

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: February 5, 2020
• Study Start: January 21, 2021
• Primary Completion: June 15, 2024
• Study Completion: June 15, 2024
• Last Updated: January 7, 2026
• Results First Posted: January 7, 2026

Record last verified: 2025-10

Locations

US (1)