Buprenorphine Plus Baclofen to Increase Analgesia in Healthy Volunteers
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Pain Threshold
研究概览
简要总结
To determine if baclofen will enhance buprenorphine analgesia for acute pain in healthy volunteers.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 years or older
- •general good health
- •English speaking
排除标准
- •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
研究组 & 干预措施
Placebo
Participants randomized to this arm will receive one dosage of Placebo as part of their second study appointment.
干预措施: Placebos (Drug)
Baclofen 5mg
Participants randomized to this arm will receive one dosage of 5 mg of Baclofen as part of their second study appointment.
干预措施: Baclofen 5 mg (Drug)
Baclofen 10mg
Participants randomized to this arm will receive one dosage of 10 mg of Baclofen as part of their second study appointment.
干预措施: Baclofen 10mg (Drug)
结局指标
主要结局
Pain Threshold
时间窗: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
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
时间窗: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
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
时间窗: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
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
时间窗: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
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.
Suprathreshold Pain Response
时间窗: 1.5 hours post-drug administration during session 2, occurs 7 ± 2 days after baseline visit
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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
Suprathreshold Pain Response
时间窗: 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
次要结局
- 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)
研究者
Karen Cropsey
Professor of Psychiatry
University of Alabama at Birmingham