The Effects of Minocycline on Opioid-induced Hyperalgesia in Opioid-Maintained Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Pain Threshold
研究概览
简要总结
Opioids are the most commonly utilized pharmacological treatment for moderate to severe pain. However, their clinical value is hindered by the development of opioid-induced hyperalgesia (OIH). OIH manifests as heightened pain sensitivity, and is an increasingly challenging drawback to the efficacy of opioid treatment. Although the mechanism of action modulating OIH is not completely understood, previous animal studies suggest that this phenomenon is a result of proinflammatory responses. Thus, administering an adjunct anti-inflammatory agent may attenuate OIH. Minocycline is one such agent; it is a tetracycline derivative antibiotic that inhibits microglia activation, nitric oxide (NO) production, and the release of pro-inflammatory cytokines and chemokines. In fact, recent evidence suggests that minocycline may attenuate the neuroinflammatory effects of opioids while enhancing their antinociceptive effects. Therefore, the investigators will determine if minocycline will mitigate OIH in methadone-maintained patients.
详细描述
Sixty completers will be recruited through the VA methadone clinic, as well as through the APT Foundation Methadone Maintenance Program. After the initial phone screening, potential subjects will undergo a comprehensive evaluation which will include medical, psychiatric, and drug use histories as well as physical, psychiatric, and laboratory examinations. Laboratory examination will include CBC, liver and thyroid function tests, serum electrolytes, BUN, creatinine, PT, PTT, urine analysis (including urine pregnancy for women) and urine toxicology screening.
Participants will be terminated from the study following opioid relapse, or use of any other psychotropic medications. If participants are noncompliant (no-show, positive urine screening, noncompliance with medication protocol/missing more than one dose of minocycline/placebo), participation will be terminated.
This double-blind, randomized clinical trial will randomize male and female veterans and non-veterans currently undergoing methadone maintenance treatment for opioid dependence to either minocycline (200mg/day) or placebo for 15 days. Upon inclusion, participants will be subjected to a pain assessment to evaluate baseline pain thresholds and tolerance: the Cold Pressor Test. An experimental treatment of either minocycline or placebo will then be initiated and maintained for 15 days. Additionally, at the beginning of Week 2 of treatment, participants will be given a Personal Digital Assistant (PDA) an HP iPAQ Pocket PC 2003 Pro that will administer Ecological Momentary Assessments (EMA). Using EMA, we can assess change in pain sensitivity, withdrawal symptoms and cognitive performance in the participants' natural environment, which increases the ecological validity of the study. Participants will be asked to return to the laboratory several times a week for the 15 consecutive days that they are taking minocycline in order to receive the study medication and to assess changes in pain thresholds and tolerance (i.e. to assess the presence, or lack thereof of hyperalgesia). Upon completion of experimental treatment, participants will be asked to return a final time to undergo pain measurement once more, to assess any changes in pain sensitivity after completion of minocycline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females, between the ages of 18 and 55
- •Diagnosed with opioid dependence and currently enrolled in methadone maintenance treatment
- •Compliant in methadone maintenance treatment and on a stable dose for two weeks or greater
- •No current dependence or abuse of any other drugs (other than tobacco or marijuana)
- •No current medical problems
- •For women:
- •not pregnant as determined by pregnancy screening;
- •not breast feeding; u
- •using acceptable birth control methods;
- •not experiencing moderate to severe premenstrual symptoms (may interfere with pain assessment);
- •regular menstrual cycles
排除标准
- •Current major psychiatric illnesses including mood, psychotic, or anxiety disorders
- •History of major medical illnesses, including liver diseases, heart disease, or other medical conditions that the physician investigator deems contraindicated for inclusion in the study
- •Current use of over-the-counter or prescription psychoactive drugs (including regular use of NSAIDS, antidepressant, anxiolytics, antipsychotics, mood stabilizers, psychostimulants) or drugs that would be expected to have major interactions with drugs to be tested, e.g., benzodiazepines, codeine, Percocet, and other opiate drugs
- •Liver function tests (ALT or AST) greater than 3x normal
- •Allergy to minocycline or other tetracyclines
研究组 & 干预措施
minocycline
200mg minocycline
干预措施: Minocycline (Drug)
Placebo
Sugar pill
干预措施: Placebo (Drug)
结局指标
主要结局
Pain Threshold
时间窗: One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)
The Cold Pressor Test (CPT) measures pain threshold (in seconds). For this test, two water coolers filled with either warm (100.04ºF/37.8ºC) or cold water (32.9-34.7ºF/0.5-1.5ºC) are used. To begin the CPT, participants first immerse their hand into the warm-water bath for 2 min. Participants are then instructed to immerse their hand into the cold water bath and report the first time they experience pain (pain threshold). Lower scores indicate lower pain threshold. Minimum score is 0 seconds, and a maximum cut-off score of 300 seconds is used to prevent tissue damage.
Pain Tolerance
时间窗: One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)
The Cold Pressor Test (CPT) measures pain threshold and pain tolerance (in seconds). For this test, two water coolers filled with either warm (100.04ºF/37.8ºC) or cold water (32.9-34.7ºF/0.5-1.5ºC) are used. To begin the CPT, participants first immerse their hand into the warm-water bath for 2 min. Participants are then instructed to immerse their hand into the cold water bath and report when the pain becomes unbearable (pain tolerance). Lower scores indicate lower pain tolerance. Minimum score is 0 seconds, and a maximum cut-off score of 300 seconds is used to prevent tissue damage.
次要结局
- Tumor Necrosis Factor Alpha (TNF-α)(Pre/post : At Screening before medication, and on Day 22 of medication)
- Ecological Momentary Assessments (EMA) - Pain(4x/day for one week)
- Ecological Momentary Assessments (EMA) - Craving(4x/day for one week)
- Ecological Momentary Assessments (EMA): SOWS(4x/day over one week)
- Digit Symbol Substitution Test(Baseline (Day 0), Pre- and 1-hour post-medication treatment on Test Days 8, 15 and 22, and at Follow-up (~Day 28)
- Sustained Attention to Response Test (SART): No-go Trials: Errors of Commission(Baseline (Day 0), Pre- and 1-hour post-medication treatment on Test Days 8, 15 and 22, and at Follow-up (~Day 28)
- Sustained Attention to Response Test (SART): Go Trials: Errors of Omission(Baseline (Day 0), Pre- and 1-hour post-medication treatment on Test Days 8, 15 and 22, and at Follow-up (~Day 28)
- Brief Pain Inventory - Short Form: Pain Severity(One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28))
- Brief Pain Inventory - Short Form: Interference(One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28))
- Profile of Mood States (POMS) Depression Subscale(One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28))
- Opioid Withdrawal Symptom Checklist (OWSC): Back Pain Item(One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28))
- Profile of Mood States (POMS) - Total Mood Disturbance(One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28))
- Short-Form McGill Pain Questionnaire (SF-MPQ): Sensory Subscale(One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28))
- Short-Form McGill Pain Questionnaire (SF-MPQ): Affective Subscale(One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28))
- Interleukin-1 Beta (IL-1β)(Pre/post : At Screening before medication, and on Day 22 of medication)
- Interleukin-6 (IL-6)(Pre/post : At Screening before medication, and on Day 22 of medication)