Acute Pain, Analgesia
Conditions
Brief summary
To determine if baclofen will enhance buprenorphine analgesia for acute pain in healthy volunteers.
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.
Interventions
DRUGPlacebos
Participants will receive placebo in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.
DRUGBaclofen 5 mg
Participants will receive 5mg of baclofen in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.
DRUGBaclofen 10mg
Participants will receive 10mg of baclofen in combination with 0.3 mg of buprenorphine to examine analgesia in acute pain tasks.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomized to one of three interventions.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Suprathreshold Pain Response | Baseline | 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 |
| Pain Threshold | 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. |
| Pain Tolerance | 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. |
| Temporal Summation of Pain | 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. |
| Conditioned Pain Modulation | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 26-item Visual Analog Scale (VAS) | 30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit | Measures subjective and physiological effects of a medication using mood states as well as questions about the dose of medication. The measure consists of 7 questions about potential drug effects, and each response is rated on a scale of 0 to 100, with 0 reflecting not at all feeling the effect and 100 reflecting very much feeling the effect. The score is the sum of the 7 responses. The minimum value is 0 and the maximum value is 700. |
| Drug Effects Questionnaire-5 | 30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit | Measures subjective experiences of a drug. The measure consists of 5 questions about the participant's experience of the drug effects, and each response is rated on a scale of 0 to 100, with 0 reflecting not at all having an experience and 100 reflecting extremely having that experience. The score is the sum of the 5 responses. The minimum value is 0 and the maximum value is 500. |
| 26-item Visual Analog Scale (Subjective Drug Effects) | 30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit | This 26-item VAS measures subjective and physiological effects of a medication using mood states as well as questions about the dose of medication. The measure consists of 7 questions about potential drug effects, and each response is rated on a scale of 0 to 100, with 0 reflecting not at all feeling the effect and 100 reflecting very much feeling the effect. The score is the sum of the 7 responses. The minimum value is 0 and the maximum value is 700. |
| Opioid Symptom Checklist | 30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit | Measures the amount and intensity of side effects after being administered an opioid. The measure consists of 14 questions about potential opioid symptoms, and each the severity of the symptom is rated on a scale from 0 to 4, with 0 reflecting not at all feeling or being bothered by the symptom and 4 reflecting being severely bothered by the symptom. The score is the sum of the 14 responses. The minimum value is 0 and the maximum value is 56. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants randomized to this arm will receive Placebo. | 6 |
| Baclofen 5mg Participants randomized to this arm will receive 5 mg of Baclofen. | 8 |
| Baclofen 10mg Participants randomized to this arm will receive 10 mg of Baclofen. | 5 |
| Total | 19 |
Baseline characteristics
| Characteristic | Total | Placebo | Baclofen 10mg | Baclofen 5mg |
|---|---|---|---|---|
| Age, Continuous | 29.58 years STANDARD_DEVIATION 11.46 | 27.17 years STANDARD_DEVIATION 12.58 | 22.8 years STANDARD_DEVIATION 2.59 | 36.63 years STANDARD_DEVIATION 11.89 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 6 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 11 Participants | 5 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 19 Participants | 6 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Female | 12 Participants | 2 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 | 0 / 5 |
| other Total, other adverse events | 1 / 6 | 0 / 8 | 0 / 5 |
| serious Total, serious adverse events | 1 / 6 | 0 / 8 | 0 / 5 |
Outcome results
Primary
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.
Time frame: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Conditioned Pain Modulation | 3.0 units on a scale | Standard Deviation 5.7 |
| Baclofen 5mg | Conditioned Pain Modulation | -10.8 units on a scale | Standard Deviation 15 |
| Baclofen 10mg | Conditioned Pain Modulation | -6.3 units on a scale | Standard Deviation 4.8 |
Primary
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.
Time frame: Baseline
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Conditioned Pain Modulation | -0.2 units on a scale | Standard Deviation 7.4 |
| Baclofen 5mg | Conditioned Pain Modulation | 2.1 units on a scale | Standard Deviation 15.5 |
| Baclofen 10mg | Conditioned Pain Modulation | -2.0 units on a scale | Standard Deviation 5.7 |
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pain Threshold | 44.62 Degrees Celsius | Standard Deviation 2.13 |
| Baclofen 5mg | Pain Threshold | 45.11 Degrees Celsius | Standard Deviation 3.04 |
| Baclofen 10mg | Pain Threshold | 43.56 Degrees Celsius | Standard Deviation 3.77 |
Primary
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.
Time frame: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pain Threshold | 43.82 Degrees Celsius | Standard Deviation 2.46 |
| Baclofen 5mg | Pain Threshold | 43.95 Degrees Celsius | Standard Deviation 2.7 |
| Baclofen 10mg | Pain Threshold | 42.06 Degrees Celsius | Standard Deviation 3.14 |
Primary
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.
Time frame: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pain Tolerance | 47.84 Degrees Celsius | Standard Deviation 1.86 |
| Baclofen 5mg | Pain Tolerance | 47.70 Degrees Celsius | Standard Deviation 2.2 |
| Baclofen 10mg | Pain Tolerance | 46.36 Degrees Celsius | Standard Deviation 2.56 |
Primary
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.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pain Tolerance | 48.17 Degrees Celsius | Standard Deviation 1.52 |
| Baclofen 5mg | Pain Tolerance | 46.84 Degrees Celsius | Standard Deviation 2 |
| Baclofen 10mg | Pain Tolerance | 47.34 Degrees Celsius | Standard Deviation 2.11 |
Primary
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
Time frame: Baseline
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Suprathreshold Pain Response | 42.5 units on a scale | Standard Deviation 20.4 |
| Baclofen 5mg | Suprathreshold Pain Response | 54.2 units on a scale | Standard Deviation 34.7 |
| Baclofen 10mg | Suprathreshold Pain Response | 53.4 units on a scale | Standard Deviation 37.6 |
Primary
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
Time frame: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Suprathreshold Pain Response | 36.0 units on a scale | Standard Deviation 15.2 |
| Baclofen 5mg | Suprathreshold Pain Response | 68.8 units on a scale | Standard Deviation 20.8 |
| Baclofen 10mg | Suprathreshold Pain Response | 54.0 units on a scale | Standard Deviation 30.7 |
Primary
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.
Time frame: Baseline
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Temporal Summation of Pain | 43.2 units on a scale | Standard Deviation 8 |
| Baclofen 5mg | Temporal Summation of Pain | 48.4 units on a scale | Standard Deviation 35.5 |
| Baclofen 10mg | Temporal Summation of Pain | 60.25 units on a scale | Standard Deviation 35.3 |
Primary
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.
Time frame: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Temporal Summation of Pain | 47.6 units on a scale | Standard Deviation 17.5 |
| Baclofen 5mg | Temporal Summation of Pain | 64.5 units on a scale | Standard Deviation 23 |
| Baclofen 10mg | Temporal Summation of Pain | 36.7 units on a scale | Standard Deviation 23.6 |
Secondary
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. The measure consists of 7 questions about potential drug effects, and each response is rated on a scale of 0 to 100, with 0 reflecting not at all feeling the effect and 100 reflecting very much feeling the effect. The score is the sum of the 7 responses. The minimum value is 0 and the maximum value is 700.
Time frame: 30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 26-item Visual Analog Scale (Subjective Drug Effects) | 180.7 units on a scale | Standard Deviation 94.3 |
| Baclofen 5mg | 26-item Visual Analog Scale (Subjective Drug Effects) | 50.4 units on a scale | Standard Deviation 88.5 |
| Baclofen 10mg | 26-item Visual Analog Scale (Subjective Drug Effects) | 120.2 units on a scale | Standard Deviation 76.9 |
Secondary
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. The measure consists of 7 questions about potential drug effects, and each response is rated on a scale of 0 to 100, with 0 reflecting not at all feeling the effect and 100 reflecting very much feeling the effect. The score is the sum of the 7 responses. The minimum value is 0 and the maximum value is 700.
Time frame: 30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 26-item Visual Analog Scale (VAS) | 180.7 units on a scale | Standard Deviation 94.3 |
| Baclofen 5mg | 26-item Visual Analog Scale (VAS) | 50.4 units on a scale | Standard Deviation 88.5 |
| Baclofen 10mg | 26-item Visual Analog Scale (VAS) | 120.2 units on a scale | Standard Deviation 76.9 |
Secondary
Drug Effects Questionnaire-5
Measures subjective experiences of a drug. The measure consists of 5 questions about the participant's experience of the drug effects, and each response is rated on a scale of 0 to 100, with 0 reflecting not at all having an experience and 100 reflecting extremely having that experience. The score is the sum of the 5 responses. The minimum value is 0 and the maximum value is 500.
Time frame: 30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
Population: Data were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Drug Effects Questionnaire-5 | 168.8 units on a scale | Standard Deviation 106.7 |
| Baclofen 5mg | Drug Effects Questionnaire-5 | 101.1 units on a scale | Standard Deviation 76 |
| Baclofen 10mg | Drug Effects Questionnaire-5 | 103.8 units on a scale | Standard Deviation 65.9 |
Secondary
Opioid Symptom Checklist
Measures the amount and intensity of side effects after being administered an opioid. The measure consists of 14 questions about potential opioid symptoms, and each the severity of the symptom is rated on a scale from 0 to 4, with 0 reflecting not at all feeling or being bothered by the symptom and 4 reflecting being severely bothered by the symptom. The score is the sum of the 14 responses. The minimum value is 0 and the maximum value is 56.
Time frame: 30 minutes post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Opioid Symptom Checklist | 4.67 units on a scale | Standard Deviation 4.08 |
| Baclofen 5mg | Opioid Symptom Checklist | 0.75 units on a scale | Standard Deviation 1.39 |
| Baclofen 10mg | Opioid Symptom Checklist | 0.60 units on a scale | Standard Deviation 0.54 |