使用α-肾上腺素能药物可乐定和多沙唑嗪治疗创伤后应激障碍中的噩梦：一项II期随机、双盲、安慰剂对照平行组研究（ClonDo试验）方案

Treating nightmares in post-traumatic stress disorder with the α-adrenergic agents clonidine and doxazosin: protocol for a phase II randomised, double-blind, placebo-controlled parallel-group study (ClonDoTrial).

作者信息

Roepke Stefan, Schoofs Nikola, Priebe Kathlen, Wuelfing Felix, Roehle Robert, Maslahati Tolou, Stieglbauer Katharina, Biedermann Sarah, Schaefer Ingo, Gallinat Jürgen, Ethofer Thomas, Fallgatter Andreas J, Hanewald Bernd, Mulert Christoph, Schmahl Christian, Otte Christian, Koglin Stefanie

机构信息

Charité-Universitätsmedizin Berlin, corporate member of of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Berlin, Germany

Charité-Universitätsmedizin Berlin, corporate member of of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus St. Hedwig Hospital, Department of Psychiatry and Psychotherapy, Berlin, Germany.

出版信息

BMJ Open. 2025 Aug 5;15(8):e098161. doi: 10.1136/bmjopen-2024-098161.

DOI:10.1136/bmjopen-2024-098161

PMID:40764082

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12336504/

Abstract

INTRODUCTION

Intrusive nightmares are a hallmark symptom of post-traumatic stress disorder (PTSD), contributing significantly to psychiatric comorbidities, impaired physical health and diminished social functioning. Currently, no pharmacological treatments are specifically approved for managing PTSD-related nightmares. However, emerging evidence suggests that adrenoceptor-targeting agents may offer therapeutic potential. Notably, clonidine and doxazosin have demonstrated efficacy in reducing PTSD-associated nightmares, as indicated by findings from open-label studies and small randomised controlled trials.

METHODS AND ANALYSIS

This study is a multicentre, double-blind, randomised (1:1:1), placebo-controlled, parallel-group interventional trial. A total of 189 eligible patients will be randomly assigned to receive clonidine, doxazosin or placebo, with a once-daily oral dose administered at bedtime for 10 weeks. The primary efficacy endpoint is the Clinician-Administered PTSD Scale B2 score at week 10, which measures the frequency and intensity of nightmares. Secondary efficacy endpoints include other PTSD-specific symptoms. Additionally, the safety of clonidine and doxazosin will be assessed.

ETHICS AND DISSEMINATION

The study was approved by the Ethics Committee of the State of Berlin (Ethik-Kommission des Landes Berlin) (Reference: 21-683-Haupt-IV E 13), on 14 March 2022 and by the relevant federal authority, the Bundesinstitut für Arzneimittel und Medizinprodukte, reference 4044931. The study was conducted in accordance with the relevant guidelines and regulations. The study results will be published in peer-reviewed journals and presented at both national and international conferences.

TRIAL REGISTRATION NUMBER

NCT05360953, EudraCT 2021-000319-21.

摘要

引言

侵入性噩梦是创伤后应激障碍（PTSD）的标志性症状，对精神共病、身体健康受损和社会功能下降有重大影响。目前，尚无专门获批用于治疗与PTSD相关噩梦的药物治疗方法。然而，新出现的证据表明，针对肾上腺素能受体的药物可能具有治疗潜力。值得注意的是，可乐定和多沙唑嗪已显示出在减少与PTSD相关噩梦方面的疗效，开放标签研究和小型随机对照试验的结果表明了这一点。

方法与分析

本研究是一项多中心、双盲、随机（1:1:1）、安慰剂对照、平行组干预试验。总共189名符合条件的患者将被随机分配接受可乐定、多沙唑嗪或安慰剂，每晚睡前口服一次，持续10周。主要疗效终点是第10周时临床医生评定的PTSD量表B2评分，该评分衡量噩梦的频率和强度。次要疗效终点包括其他PTSD特异性症状。此外，将评估可乐定和多沙唑嗪的安全性。

伦理与传播

该研究于2022年3月14日获得柏林州伦理委员会（Ethik-Kommission des Landes Berlin）（参考编号：21-683-Haupt-IV E 13）以及相关联邦机构德国药品和医疗器械管理局（Bundesinstitut für Arzneimittel und Medizinprodukte）的批准，参考编号4044931。该研究按照相关指南和规定进行。研究结果将发表在同行评审期刊上，并在国内和国际会议上展示。