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Buprenorphine Plus Baclofen to Increase Analgesia in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04251819
Recruitment Status : Not yet recruiting
First Posted : February 5, 2020
Last Update Posted : August 19, 2020
Sponsor:
Information provided by (Responsible Party):
Karen Cropsey, University of Alabama at Birmingham

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

Condition or disease Intervention/treatment Phase
Acute Pain Analgesia Drug: Placebos Drug: Baclofen 5 MG Drug: Baclofen 10mg Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be randomized to one of three interventions.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Buprenorphine Plus Baclofen to Increase Analgesia in Healthy Volunteers
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Participants randomized to this arm will receive Placebo.
Drug: Placebos
Participants will receive placebo in combination with 4mg 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 4mg 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 4mg of buprenorphine to examine analgesia in acute pain tasks.




Primary Outcome Measures :
  1. Pain Threshold [ Time Frame: Baseline ]
    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.

  2. Pain Threshold [ Time Frame: Baseline through one week ]
    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.

  3. Pain tolerance [ Time Frame: Baseline ]
    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.

  4. Pain tolerance [ Time Frame: Baseline through one week ]
    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.

  5. Temporal summation of pain [ Time Frame: Baseline ]
    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.

  6. Temporal summation of pain [ Time Frame: Baseline through one week ]
    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.

  7. Conditioned pain modulation [ Time Frame: Baseline ]
    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.

  8. Conditioned pain modulation [ Time Frame: Baseline through one week ]
    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.


Secondary Outcome Measures :
  1. Opioid Symptom Checklist [ Time Frame: One to seven days post baseline ]
    Lists True-False questions measuring opioid effects.

  2. McGill Pain Questionnaire-Short Form [ Time Frame: One to seven days post baseline ]
    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.

  3. 26-item Visual Analog Scale (VAS) [ Time Frame: One to seven days post baseline ]
    Measures subjective and physiological effects of a medication using mood states as well as questions about the dose of medication.

  4. Drug Effects Questionnaire-5 [ Time Frame: One to seven days post baseline ]
    Assesses drug effects and uses VAS ratings from "Not at all" to "Very much."



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  • Cognitive impairment or psychiatric disorder requiring treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04251819


Contacts
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Contact: Karen L Cropsey, Psy.D. 2059754204 kcropsey@uab.edu
Contact: Keith Chichester, B.A. 2059757809 krc80@uab.edu

Locations
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United States, Alabama
University of Alabama, Birmingham
Birmingham, Alabama, United States, 35209
Contact: Keith Chichester, B.A.    205-975-7809    krc80@uab.edu   
Contact: Mickeah Hugley, B.S.    205-975-7809    mickeahhugley@uabmc.edu   
Principal Investigator: Karen Cropsey, Psy.D.         
Sponsors and Collaborators
University of Alabama at Birmingham
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Responsible Party: Karen Cropsey, Professor of Psychiatry, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT04251819    
Other Study ID Numbers: 300004505
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: August 19, 2020
Last Verified: August 2020

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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
Additional relevant MeSH terms:
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Acute Pain
Neurologic Manifestations
Pain
Baclofen
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
GABA-B Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action