Pilot Study of Opioid-receptor Antagonists to Reduce Pain and Inflammation among HIV-Infected Persons with Alcohol Problems

阿片受体拮抗剂减轻有酗酒问题的艾滋病毒感染者疼痛和炎症的初步研究

• 批准号: 10019309
• 负责人: JEFFREY H. SAMET
• 金额: $ 35.46万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019309
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Address; Age; Alcohol abuse; Alcohol consumption; Alcohol withdrawal syndrome; Alcoholic beverage heavy drinker; Alcohols; Analgesics; Animals; Anti-Inflammatory Agents; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Caring; Chronic; Clinical; Disease; Dose; Double-Blind Method; Epidemic; Etiology; Europe; FDA approved; Feasibility Studies; Future; HIV; HIV Infections; Health; Heavy Drinking; High Prevalence; Human; Hyperalgesia; Hypertension; Inflammation; Inflammatory; Interleukin-6; Lead; Life Expectancy; Measures; Mediating; Mental Health; Naltrexone; National Institute on Alcohol Abuse and Alcoholism; Neuroglia; Neuropathy; Opioid; Opioid Antagonist; Opioid Receptor; Opioid agonist; Outcome; Pain; Pain management; Patient Self-Report; Patients; Persons; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Phase; Pilot Projects; Placebos; Play; Population; Prevalence Study; Procedures; Property; Provider; Randomized; Regulation; Research; Research Proposals; Risk Behaviors; Role; Russia; Safety; Severities; Surveys; T-Lymphocyte; TNF gene; Testing; Time; Up-Regulation; Viral Load result; Work; addiction; alcohol abuse therapy; alcohol misuse; alcohol use disorder; antiretroviral therapy; arm; barrier to care; central pain; central sensitization; chronic pain; chronic painful condition; cohort; comorbidity; cytokine; design; effective therapy; endogenous opioids; high risk behavior; improved; inflammatory marker; innovation; nalmefene; non-opioid analgesic; novel; opioid agonist therapy; opioid epidemic; opioid use; opioid use disorder; pain reduction; patient oriented; placebo controlled study; premature; reduced alcohol use; sex; therapy adherence

Pain is a common co-morbidity for HIV-infected patients. Prevalence studies suggest that, on average, half of all HIV-infected persons suffer pain. Chronic pain can lead to heavy alcohol use among HIV-infected persons, which may in turn be a barrier to treatment/control of HIV and contribute to spread of HIV. Thus there is an urgent need to address pain among persons with HIV. Opioid receptor antagonists such as naltrexone and nalmefene, which are licensed for treatment of alcohol use disorders, show promise as being effective and safe treatments for chronic pain among persons with HIV. This study will pilot test novel pharmacotherapies (opioid receptor antagonists) to improve chronic pain among HIV-infected heavy drinkers, and will explore the hypothesis that the mechanism of action for improving pain is through decreased inflammation. The specific aims of the research are: UH2/Aim 1: To assess the feasibility, tolerability and safety of using opioid receptor antagonists (low-dose naltrexone and nalmefene) to treat pain among HIV-infected persons with heavy alcohol use and chronic pain; UH3/Aim 2: to perform a 3-arm pilot randomized, double-blinded, placebo-controlled study of low-dose naltrexone and nalmefene vs. placebo among HIV-infected persons with heavy alcohol use and chronic pain to provide estimates of their effects on: 1) pain (both self-reported and experimental/cold pressor test; 2) inflammation (i.e., levels of inflammatory cytokines IL-6 and TNF-α); and 3) measures of HIV control (CD4 count and viral load). The results of this study will provide preliminary information (tolerability, effect size, etc.) to design a larger RCT of low-dose naltrexone and/or nalmefene for chronic pain among persons with heavy alcohol use. We choose to conduct this research in St. Petersburg, Russia, given that: 1) nalmefene is licensed in Russia, but not currently in the US; 2) patients are seldom on chronic opioids (which are contraindicated to use with opioid receptor antagonists) due to the unavailability of opioid agonist therapy for addiction and restricted use of opioids for pain; and 3) a high prevalence of heavy drinking and HIV exists in Russia. Addressing chronic pain is a high priority for patients with HIV, and therefore this application is highly “patient-centered” as well as innovative. Given the US epidemic of opioid use disorders, new pharmacotherapies without addictive potential are desperately needed for HIV-infected persons with chronic pain and alcohol problems.

疼痛是HIV感染患者的常见合并症。流行研究表明，平均一半 所有感染HIV的人都会遭受痛苦。慢性疼痛会导致艾滋病毒感染者大量使用酒精， 反过来，这可能是艾滋病毒治疗/控制的障碍，并导致艾滋病毒的传播。有一个 迫切需要解决艾滋病毒患者的疼痛。阿片类药物接收器拮抗剂，例如纳曲酮和 纳米芬（Nalmefene 艾滋病毒患者的慢性疼痛的安全治疗。这项研究将试行新的药物治疗 （阿片类受体拮抗剂）改善艾滋病毒感染的重量饮酒者的慢性疼痛，并将探索 假设通过减少炎症来改善疼痛的作用机理。具体 研究的目的是：UH2/AIM 1：评估使用阿片类药物接收器的可行性，耐受性和安全性 拮抗剂（低剂量纳曲酮和Nalmefene）治疗艾滋病毒感染的人中疼痛 使用和慢性疼痛； UH3/AIM 2：执行3臂飞行员随机，双盲，安慰剂对照 在艾滋病毒感染者中，低剂量纳曲酮和纳米芬与安慰剂的研究 和慢性疼痛以估计其对以下影响：1）疼痛（自我报告和实验/冷 施加测试； 2）炎症（即炎性细胞因子IL-6和TNF-α的水平）； 3）艾滋病毒的措施 控制（CD4计数和病毒载荷）。这项研究的结果将提供初步信息（耐受性， 效应大小等）设计较大的低剂量纳曲酮和/或纳米芬的较大RCT，以使其慢性疼痛 大量饮酒的人。我们选择在俄罗斯圣彼得堡进行这项研究：1） Nalmefene在俄罗斯获得许可，但目前不在美国； 2）患者很少使用慢性阿片类药物（这 由于阿片类药物疗法无法获得，禁忌与阿片类药物接收器拮抗剂一起使用） 成瘾和限制使用阿片类药物来疼痛； 3）大量饮酒和艾滋病毒的高流行率 俄罗斯。解决慢性疼痛是艾滋病毒患者的重点，因此该应用高度高 “以患者为中心”和创新。考虑到美国阿片类药物使用障碍的流行，新的 对于患有慢性的艾滋病毒感染者，迫切需要没有其他潜力的药物治疗 疼痛和酒精问题。