Prazosin for Noncombat Trauma PTSD

哌唑嗪治疗非战斗创伤创伤后应激障碍

• 批准号: 7226651
• 负责人: MURRAY A RASKIND
• 金额: $ 32.45万
• 依托单位: SEATTLE INST FOR BIOMEDICAL/CLINICAL RES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-18 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7226651
• 关键词: Adrenergic Antagonists; Adverse effects; Adverse event; Blood; Brain; Chronic; Clinical; Clinical Trials; Count; Distress; Dose; Double-Blind Method; Dreams; Dropout; Female; Frequencies; Functional disorder; Lead; Measures; Monitor; Nightmare; Numbers; Outcome Measure; Paroxetine; Personal Satisfaction; Persons; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Population; Post-Traumatic Stress Disorders; Prazosin; Principal Investigator; Psychotherapy; Quality of life; Randomized; Recurrence; Residual state; Resistance; Score; Secondary to; Selective Serotonin Reuptake Inhibitor; Severities; Severity of illness; Signs and Symptoms; Sleep; Sleep disturbances; Standards of Weights and Measures; Symptoms; Testing; Time; Titrations; Trauma; Veterans; Week; alpha-1 adrenergic receptors; day; depressive symptoms; design; discontinuation trial; efficacy trial; falls; functional disability; impression; indexing; male; pill; programs

DESCRIPTION (provided by applicant): We propose a double-blind placebo-controlled augmentation trial of the generically available alpha-1 adrenergic antagonist prazosin in chronic posttraumatic stress disorder (PTSD) caused by noncombat ("civilian") trauma. Primary target PTSD symptoms will be residual distressing trauma-related nightmares and sleep disturbance that persist despite a trial of the selective serotonin reuptake inhibitor (SSRI) paroxetine. Although several SSRIs are FDA-approved for PTSD, SSRIs (and other drugs) often are not helpful for these very distressing nighttime PTSD Symptoms. Preliminary studies in older male combat veterans with chronic PTSD demonstrated that prazosin (the only available alpha-1 antagonist that crosses from blood into brain) eliminated or Substantially reduced previously treatment resistant trauma-related nightmares and sleep disturbance that had been distressing and debilitating for many years. Prazosin also reduced overall illness severity and functional impairment, and was well tolerated. These beneficial prazosin effects are consistent with involvement of increased responsiveness of brain alpha-1 adrenergic receptors in PTSD pathophysiology. Here we will determine if these encouraging prazosin results also can be demonstrated in the generally younger and predominantly female population of persons with noncombat trauma PTSD who continue to suffer from residual distressing trauma related nightmares and sleep disturbance despite standard PTSD treatment. In a double-blind placebo-controlled parallel group 8-week clinical trial of prazosin augmentation (following a 12-week "lead-in" of standard SSRI plus manualized psychotherapy treatment) the following hypotheses will be tested: Hypothesis 1: Persons with PTSD manifested by residual distressing trauma-related nightmares and sleep disturbance (despite SSRI treatment) randomized to prazosin augmentation will manifest a greater reduction in trauma related nightmares and sleep disturbance than those randomized to placebo augmentation. Hypothesis 2: Persons with PTSD manifested by residual distressing trauma-related nightmares and sleep disturbance (despite SSRI treatment) randomized to prazosin augmentation will manifest greater improvement in overall global PTSD severity and function than those randomized to placebo augmentation. Hypothesis 3: The time to study discontinuation ("dropout") due to unacceptable adverse effects will not differ between PTSD subjects randomized to prazosin augmentation and those randomized to placebo augmentation. Primary outcome measures will be the Clinician Administered PTSD Scale (CAPS) Recurrent Distressing Dreams item, the Pittsburgh Sleep Quality Index, and the Clinical Global Impression of Change. Additional outcome measures will be the total CAPS score, the CAPS Difficulty Falling or Staying Asleep item, the three CAPS subscales (Reexperiencing/Intrusions, Avoidance/Numbing, and Hyperarousal), measures of nightmare quality and frequency, depressive signs and symptoms, and quality of life. Number of study days completed and adverse events also will be compared between groups.

描述（由申请人提供）：我们提出了一个双盲安慰剂对照的增强试验，一般可用的α-1肾上腺素能拮抗剂哌唑嗪在慢性创伤后应激障碍（PTSD）引起的非战斗（“平民”）创伤。主要目标PTSD症状将是残留的痛苦的创伤相关的噩梦和睡眠障碍，尽管选择性5-羟色胺再摄取抑制剂（SSRI）帕罗西汀试验持续存在。虽然几种SSRIs被FDA批准用于PTSD，但SSRIs（和其他药物）通常对这些非常令人痛苦的夜间PTSD症状没有帮助。在患有慢性PTSD的老年男性退伍军人中进行的初步研究表明，哌唑嗪（唯一可用的从血液进入大脑的α-1拮抗剂）消除或大大减少了以前治疗抵抗性创伤相关的噩梦和睡眠障碍，这些噩梦和睡眠障碍多年来一直令人痛苦和虚弱。哌唑嗪也降低了整体疾病的严重程度和功能障碍，耐受性良好。这些有益的哌唑嗪作用与PTSD病理生理学中脑α-1肾上腺素能受体反应性增加的参与一致。在这里，我们将确定这些令人鼓舞的哌唑嗪的结果是否也可以在一般年轻和主要是女性的非战斗创伤PTSD患者中得到证实，这些患者尽管接受了标准的PTSD治疗，但仍继续遭受残余的创伤相关噩梦和睡眠障碍。在一项为期8周的哌唑嗪强化治疗的双盲安慰剂对照平行组临床试验（在标准SSRI加手动心理治疗的12周“导入”后）中，将检验以下假设：假设1：表现为残余痛苦创伤相关噩梦和睡眠的PTSD患者 随机分配至哌唑嗪强化组的受试者（尽管进行了SSRI治疗）与随机分配至安慰剂强化组的受试者相比，在创伤相关噩梦和睡眠障碍方面表现出更大的减少。假设二：表现为残余痛苦创伤相关噩梦和睡眠障碍（尽管SSRI治疗）的PTSD患者随机接受哌唑嗪强化治疗，与随机接受安慰剂强化治疗的患者相比，总体PTSD严重程度和功能改善更大。假设三：由于不可接受的不良反应导致的研究中止（“脱落”）的时间在随机接受哌唑嗪强化治疗的PTSD受试者和随机接受安慰剂强化治疗的受试者之间没有差异。主要结果指标将是临床医生管理的PTSD量表（CAPS）复发性痛苦梦项目、匹兹堡睡眠质量指数和临床总体印象变化。额外的结果测量将是总CAPS评分、CAPS跌倒困难或保持镇静项目、三个CAPS子量表（再体验/侵入， 回避/麻木和过度觉醒），噩梦质量和频率的测量，抑郁体征和症状，以及生活质量。还将比较两组间完成的研究天数和不良事件。