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感染者常见的并发症。流行率研究表明，平均而言， 所有艾滋病毒感染者都遭受痛苦。慢性疼痛可导致艾滋病毒感染者大量饮酒， 这可能反过来成为治疗/控制HIV的障碍并促进HIV的传播。因此， 迫切需要解决艾滋病毒感染者的痛苦问题。阿片受体拮抗剂如纳洛酮和 纳美芬，被许可用于治疗酒精使用障碍，显示出有效的前景， 艾滋病毒感染者慢性疼痛的安全治疗。这项研究将对新的药物疗法进行初步测试 （阿片受体拮抗剂），以改善慢性疼痛的艾滋病毒感染的酗酒者，并将探讨 这一假说认为，改善疼痛的作用机制是通过减少炎症。具体 本研究的目的是：UH 2/目的1：评估使用阿片受体的可行性、耐受性和安全性 拮抗剂（低剂量纳洛酮和纳美芬）用于治疗重度饮酒的HIV感染者的疼痛 使用和慢性疼痛; UH 3/目的2：进行一项3组随机、双盲、安慰剂对照的初步研究 低剂量纳洛酮和纳美芬与安慰剂在重度饮酒的HIV感染者中的对比研究 和慢性疼痛，以提供其对以下方面的影响的估计：1）疼痛（自我报告的和实验性的/冷的 升压试验; 2）炎症（即，炎性细胞因子IL-6和TNF-α的水平）;和3）HIV的测量 对照（CD 4计数和病毒载量）。本研究的结果将提供初步信息（耐受性， 效果大小等）设计一项更大的低剂量纳洛酮和/或纳美芬治疗慢性疼痛的随机对照试验， 重度饮酒者。我们选择在俄罗斯彼得堡进行这项研究，因为：1） 纳美芬在俄罗斯获得许可，但目前在美国尚未获得许可; 2）患者很少使用慢性阿片类药物（ 禁忌与阿片受体拮抗剂一起使用），因为无法获得阿片受体激动剂治疗 成瘾和限制使用阿片类药物止痛;和3）大量饮酒和艾滋病毒的高流行率存在于 俄罗斯解决慢性疼痛是艾滋病毒感染者的高度优先事项，因此这种应用非常受欢迎。 “以病人为中心”，创新。鉴于美国阿片类药物使用障碍的流行， 艾滋病毒感染者迫切需要没有成瘾潜力的药物治疗， 疼痛和酒精问题