Proof of Concept Trial of Cannabis Derivatives in Neuropathic Pain.

大麻衍生物治疗神经性疼痛的概念验证试验。

• 批准号: 10426260
• 负责人: DEEPAK Cyril D'SOUZA
• 金额: --
• 依托单位: VA CONNECTICUT HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426260
• 关键词: Adherence; Adult; Adverse effects; Adverse event; Affect; Anxiety; Benefits and Risks; Biological Markers; Cannabidiol; Cannabinoids; Cannabis; Cellular Phone; Chronic; Clinical Research; Clinical Trials; Collaborations; Complications of Diabetes Mellitus; Controlled Study; Data; Dependence; Diabetes Mellitus; Dose; Double-Blind Method; Enrollment; Exercise; Fatigue; General Population; Health Care Costs; Human; Individual; Insulin; Intention; Intervention; Lead; Linear Regressions; Measures; Mediating; Medical Marijuana; Mental Depression; Methods; Modeling; Monitor; Numeric Rating Scale; Outcome; Outcome Measure; Outcomes Research; Pain; Pain Research; Pain management; Pain quality; Participant; Patients; Peripheral; Peripheral Nervous System Diseases; Pharmacotherapy; Pharmacy facility; Phase; Placebo Control; Placebos; Post-Traumatic Stress Disorders; Protocols documentation; Quality of life; Randomized; Randomized Controlled Clinical Trials; Reporting; Research; Research Personnel; Risk; Safety; Sampling; Serious Adverse Event; Single-Blind Study; Site; Sleeplessness; Standardization; Statistical Models; Structure; Surveys; Tachycardia; Tapentadol; Tetrahydrocannabinol; Therapeutic; Titrations; Traumatic Brain Injury; Treatment Cost; Treatment Efficacy; Treatment outcome; United States; United States Department of Veterans Affairs; Veterans; Withdrawal Symptom; Work; abuse liability; active method; adverse outcome; antinociception; arm; associated symptom; cannabis withdrawal; chronic pain; cognitive function; comorbidity; cooperative study; daily pain; design; diabetic; diabetic patient; diagnostic criteria; diaries; disability; duloxetine; efficacy evaluation; emotional functioning; expectation; fall risk; four-arm study; glycemic control; health related quality of life; high risk; improved; interest; intervention effect; marijuana use; marijuana use disorder; marijuana user; medication compliance; non-opioid analgesic; opioid epidemic; opioid use; pain outcome; pain reduction; pain relief; pain scale; pain score; pain-related disability; painful neuropathy; pharmacologic; phase 2 study; phase III trial; pill; preclinical study; pregabalin; primary outcome; programs; psychiatric comorbidity; randomized trial; recruit; safety outcomes; satisfaction; secondary analysis; secondary outcome; side effect; substance use; synthetic cannabinoid; treatment adherence; treatment arm; trial comparing; urinary; vehicular accident

ABSTRACT Chronic pain is a significant burden to United States Veterans and is a particular concern for Veterans with diabetes. Diabetic Veterans have a higher risk of chronic diabetic peripheral neuropathy (CDNP) than civilians with diabetes, and CDNP is more disabling for Veterans than it is for civilians. Frontline treatment for CDNP, including enhanced glycemic control, exercise, and pharmacotherapies, show inconsistent outcomes for individuals with CDNP due to poor adherence and side effects. The ongoing opioid crisis has led to significant interest in safe and effective alternatives for pain control, and there is a significant need for research on desirable options for pain control that are likely to improve treatment adherence and outcomes. Veterans groups and Veterans Affairs clinicians have expressed significant interest in cannabis and its principal constituents (delta-9-tetrathydrocannabinol, THC; cannabidiol, CBD) for pain management, but the extant research describing the potential risks and benefits of cannabis for pain is weak. The present study represents the first significant effort to examine the potential benefits and risks of cannabinoids for Veterans with CDNP through a collaboration between a nationally-recognized cannabis research expert (Dr. D’Souza), a Veteran chronic pain research expert (Dr. McGeary), the Hines Cooperative Studies Program Coordinating Center, and the Albuquerque Cooperative Studies Program Clinical Research Pharmacy Coordinating Center. This research collaboration was developed to meaningfully expand on the extant research using a 4-arm, randomized, double-blind, placebo-controlled, parallel group design. This randomized trial was developed as a proof of concept study to determine if cannabis constituents (THC, CBD) or their combination (THC+CBD) are superior to placebo in reducing pain in Veterans with CDNP. Additionally, this will weigh the safety and tolerability of the interventions against the identified efficacy. The investigators will work with 5 VAMCs to recruit a sample of 320 adult Veterans who meet diagnostic criteria for high-impact CDNP, are on stable treatment(s) for CDNP, are not current cannabis users and who do not meet diagnostic criteria for Cannabis Use Disorder. Enrolled Veterans will be randomly assigned to one of four study arms: 1) 5 mg THC P.O BID; 2) 400 mg CBD P.O BID; 3) 5mg THC + 5 mg CBD P.O BID; or 4) placebo P.O BID. Participants will complete a 2-week titration phase (to minimize side effects and improve tolerability) followed by 4 weeks on the target treatment dose and a subsequent 2-week down titration (to minimize cannabis withdrawal symptoms). The primary outcome of this research is mean change in Numeric Rating Scale of pain (NRS) based on a standardized pain diary completed three times daily producing an average daily pain score. Secondary outcomes include measures of pain quality, functioning/disability, health-related quality of life, perceived improvement and treatment satisfaction, emotional functioning, and safety. The investigators will assess treatment adherence using urinary biomarkers, weekly pill counts, and daily cell phone assisted remote outcomes adherence (CAROMA) contacts that will also assess medication adherence and pain diary entries. Data will be analyzed using a 3-level hierarchical mixed-effects linear regression model. If successful, the proposed study will offer the highest quality proof of concept data for the use of cannabis to treat CDNP in U.S. Veterans. These data will provide meaningful guidance on additional studies of cannabis for Veterans with pain and have a high likelihood of also benefiting civilians with CDNP.

抽象的 慢性疼痛对美国退伍军人来说是一个重要的伯恩顿 糖尿病。糖尿病退伍军人的慢性糖尿病外周神经病（CDNP）的风险高于平民 与糖尿病相比，对于退伍军人而言，糖尿病和CDNP比平民更具残疾人。 CDNP的一线治疗 包括增强的血糖控制，运动和药物治疗，显示出不一致的结果 由于依从性差和副作用而导致CDNP的个体。正在进行的阿片类药物危机导致了重大 对安全有效替代疼痛控制的兴趣，并且非常需要研究 可能改善治疗依从性和结局的疼痛控制的理想选择。退伍军人 团体和退伍军人事务临床医生对大麻及其校长表示重大兴趣 用于疼痛管理的组成量（Delta-9-tetrathydrocanbinol，THC； CANBIDIOL，CBD），但广泛 描述大麻对疼痛的潜在风险和益处的研究很弱。本研究代表 检查CDNP退伍军人的大麻素的潜在益处和风险的首要努力 通过一位经验丰富的大麻研究专家（D'Souza博士）之间的合作 慢性疼痛研究专家（McGeary博士），Hines合作研究计划协调中心和 阿尔伯克基合作研究计划临床研究药房协调中心。这 开发研究合作是为了有意义地扩展使用4臂研究的范围研究 随机，双盲，安慰剂对照，平行组设计。这项随机试验是作为一个 确定大麻构成（THC，CBD）或其组合（THC+CBD）的概念证明是 在减轻CDNP退伍军人的疼痛方面，优于安慰剂。此外，这将权衡安全性和 干预措施对确定效率的耐受性。调查人员将与5个VAMC合作 招募符合高影响力CDNP诊断标准的320名成年退伍军人的样本 CDNP的治疗不是目前的大麻使用者，并且不符合大麻的诊断标准 使用障碍。入学的退伍军人将被随机分配到四个研究臂之一：1）5 mg thc p.o bid; 2） 400 mg CBD P.O出价; 3）5mg THC + 5mg CBD P.O BID;或4）安慰剂p.o出价。参与者将完成 2周的滴定阶段（以最大程度地减少副作用并提高耐受性），然后在目标上进行4周 治疗剂量和随后的2周下滴定（以最大程度地减少大麻戒断症状）。 这项研究的主要结果是基于A的数字评级量表（NR）的平均变化 标准化疼痛日记每天完成3次，每天平均疼痛评分。次要 结果包括疼痛质量，功能/残疾，与健康相关的生活质量的度量，感知到 改善和治疗满意度，情绪功能和安全性。调查人员将评估 使用尿生物标志物，每周药丸计数和每日手机辅助遥控器的治疗依从性 结果依从性（碳瘤）接触，还将评估药物依从性和疼痛日记条目。 将使用3级层次混合效应线性回归模型分析数据。如果成功， 拟议的研究将提供最高质量的概念证明数据，用于使用大麻在美国治疗CDNP 退伍军人。这些数据将为有痛苦的退伍军人的大麻研究提供有意义的指导 并且很有可能使CDNP平民受益。