Chronic Postconcussive Headache: A Placebo-Controlled Treatment Trial of Prazosin

慢性脑震荡后头痛：哌唑嗪安慰剂对照治疗试验

• 批准号: 9260709
• 负责人: Cynthia L Mayer
• 金额: --
• 依托单位: VA PUGET SOUND HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9260709
• 关键词: Academic Training; Address; Adrenergic Agents; Adverse effects; Affect; Afghanistan; Alcohol consumption; Analgesic Overuse Headaches; Analgesics; Benign; Blast Cell; Board Certification; Brain Concussion; Brain Injuries; Case Series; Chronic; Clinical; Clinical Trials; Cognition; Cognitive; Comorbidity; Competence; Contracts; Controlled Clinical Trials; Controlled Study; Craniocerebral Trauma; Data; Data Analyses; Department of Defense; Development; Development Plans; Discipline of Nuclear Medicine; Distress; Dose; Double-Blind Method; Education; Elements; Evaluation; Follow-Up Studies; Fostering; Foundations; Frequencies; Functional disorder; Funding; Future; General Population; Generic Drugs; Goals; Grant; Growth; Guidelines; Headache; Healthcare Systems; High Prevalence; Home environment; Hour; Human; Injury; International; Intractable Pain; Iraq; Learning; Legal patent; Length; Longevity; Measures; Medical; Mental Depression; Mental disorders; Mentors; Methods; Migraine; Military Personnel; Moods; Neurologic; Neurology; Opiates; Opioid; Oral; Outcome; Outcome Measure; Participant; Pathway interactions; Patients; Pharmaceutical Preparations; Placebo Control; Placebos; Population; Positioning Attribute; Positron-Emission Tomography; Post-Traumatic Stress Disorders; Prazosin; Price; Private Sector; Prophylactic treatment; Public Health; Publishing; Quality of life; Randomized; Refractory; Rehabilitation therapy; Reporting; Research; Research Design; Research Personnel; Resistance; Risk; Role; Services; Severities; Sleep; Social Welfare; Societies; Solid; Source; Symptoms; Syndrome; System; Target Populations; Testing; Tracer; Training; Training Programs; Veterans; Workplace; Writing; alcohol craving; alpha-1 adrenergic receptors; alpha-adrenergic receptor; apprenticeship; base; career; career development; chronic pain; combat; cost; design; disability; economic incentive; experience; health related quality of life; interest; mild traumatic brain injury; noradrenergic; open label; placebo controlled study; power analysis; primary outcome; programs; prophylactic; public health relevance; screening; secondary outcome; service member; skills; treatment duration; treatment trial

DESCRIPTION: Background and Study Objective: Posttraumatic headaches (PTHAs) following mild traumatic brain injury (mTBI) are common, often refractory to standard therapies, and can progress to become a debilitating chronic pain syndrome. Studies of the centrally acting alpha-1 adrenergic receptor (AR) blocker prazosin for treating combat-related posttraumatic stress disorder (PTSD) have coincidentally shown evidence for ameliorating co- morbid headaches (HAs). A large open-label case series and anecdotal reports have additionally noted beneficial effect of prazosin on HAs, in particular, those following blast mTBI. The objective of the proposed study is to rigorously evaluate the efficacy of prazosin for prophylaxis of chronic PTHA following combat mTBI. Study Design and Methods: This is a double-blind placebo-controlled clinical trial based on International Headache Society Guidelines for migraine prophylactic drug studies. The trial length is 16 weeks, including a 4-week pre-treatment screening period followed by a 12-week treatment period, in which participants will be randomized 1:1 to prazosin or placebo. Primary outcome measures will include change from baseline in HA frequency and cumulative HA hours. Secondary outcome measures will include change in other HA measures, PTSD symptoms, sleep quality, depression, alcohol use, cognition, health-related quality of life, and global clinical status. Based on a power analysis for the primary outcome measures, we will need 37 subjects per group to achieve 80% power using a 5% Type I error level. Career Goals: My primary career goal is to combine research and service, working with a population whose needs are diverse and challenging. The VA Healthcare System provides an excellent opportunity for this. Neurologic issues are of particular relevance to Veterans, both as service-related and across the life-span. My intentions in the proposed study are to evaluate a potential treatment for a condition that significantly impacts the welfare of Veterans, as well as to lay the foundation for future studies of the pathophysiology of PTHAs. The demonstration of favorable effects of prazosin on PTSD, sleep disruption, and likely on PTHAs suggests a common pathway involving the alpha-1 adrenergic system. Characterization of this pathway would be expected to foster development of more precisely targeted treatments. For example, HAs are a leading cause for opioid prescribing, with opiate use becoming a public health issue for both the Department of Defense and the VA. Identifying noradrenergic mechanisms in PTHAs could serve as a foundation for efforts to reduce the use of opiates for treating this condition. The Northwest Network Mental Illness Research, Education, and Clinical Center has taken a multi-faceted approach to addressing some of these questions, with several related ongoing studies, including development of a PET tracer for alpha ARs. A long-term goal is to integrate my background in nuclear medicine/PET imaging with the expertise I hope to develop in TBI and HA neurology. Key Elements of the Research Career Development Plan: (1) Develop competence in designing and conducting human clinical trials; (2) Obtain a strong conceptual base for current and future research efforts through didactic and other training; (3) Gain experience in analyzing/interpreting results and publishing/presenting findings; (4) Learn grantsmanship skills; (5) Develop solid clinical expertise in the subspecialties of mTBI and HA evaluation and management; (6) Obtain Board Certification in neurology. Mentoring/Training Plan: My team of mentors can provide the depth of clinical training I need to become a HA expert and nurture my growth as a competent, independent clinical researcher though one-on-one apprenticeship training. Other elements of my training plan include: (1) A didactic training program with selected courses relevant to my current and long-term research interests; (2) Participation in seminars and educational programs relevant to TBI and HAs design and conduct of human clinical trials, and grant writing; (3) Experience in oral and written presentation of research findings.

描述： 背景和研究目标：轻度创伤性脑损伤（MTBI）后创伤后头痛（PTHA）很常见，通常对标准疗法难治性，并且可以发展成为一种使人衰弱的慢性疼痛综合征。对中央作用α-1肾上腺素能受体（AR）阻滞剂prazosin的研究，用于治疗与战斗相关的创伤后应激障碍（PTSD）的研究，偶然地证明了可以改善病态性头痛（HAS）的证据。大型的开放标签案例系列和轶事报告还指出了prazosin对爆炸MTBI的有益作用。拟议的研究的目的是严格评估prazosin在战斗MTBI后对慢性PTHA预防的疗效。研究设计和方法：这是一项基于国际头痛社会预防性药物研究指南的双盲安慰剂对照临床试验。试验长度为16周，包括为期4周的预处理筛查期，然后进行12周的治疗期，其中参与者将以1：1的方式随机分配给prazosin或安慰剂。主要结果指标将包括从基线频率和累积HA小时的变化。次要结果措施将包括其他HA措施，PTSD症状，睡眠质量，抑郁，酒精使用，认知，与健康相关的生活质量和全球临床状况的改变。基于针对主要结果指标的功率分析，我们将需要每组37名受试者使用5％I型误差水平实现80％的功率。职业目标：我的主要职业目标是将研究和服务结合起来，与人群多样化和具有挑战性的人群合作。 VA医疗保健系统为此提供了绝佳的机会。神经系统问题与退伍军人尤其相关，无论是服务有关还是在整个生命中。我在拟议的研究中的目的是评估对重大影响退伍军人福利的状况的潜在治疗 未来研究PTHA的病理生理学的基础。 pTSD对PTSD，睡眠破坏以及PTHA的有利作用的证明表明，涉及Alpha-1肾上腺素能系统的常见途径。预计该途径的表征将促进更精确的靶向治疗。例如，是阿片类药物处方的主要原因，而鸦片使用成为国防部和弗吉尼亚州的公共卫生问题。识别PTHA中的去甲肾上腺素能机制可以作为减少鸦片使用治疗这种情况的努力的基础。西北网络精神疾病研究，教育和临床中心已经采取了多方面的方法来解决其中一些问题，并进行了一些相关的持续研究，包括开发Alpha ARS的宠物示踪剂。一个长期的目标是将我的核医学/宠物成像背景与我希望在TBI和HA神经病学发展的专业知识相结合。研究职业发展计划的关键要素：（1）发展设计和进行人类临床试验的能力； （2）通过教学和其他培训获得当前和未来研究工作的强大概念基础； （3）在分析/解释结果和发布/提出发现方面获得经验； （4）学习授予技巧； （5）在MTBI和HA评估和管理的亚专业方面发展稳定的临床专业知识； （6）获得神经病学董事会认证。指导/培训计划：我的导师团队可以提供临床培训的深度，我需要成为HA专家，并通过一对一的学徒培训来培养我作为一个有能力的独立临床研究人员的成长。我的培训计划的其他要素包括：（1）与我当前和长期研究兴趣相关的选定课程的教学培训计划； （2）参加与TBI相关的研讨会和教育计划，并具有人类临床试验的设计和行为以及授予写作； （3）研究结果的口头和书面介绍经验。