{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T22:52:10Z","timestamp":1773615130947,"version":"3.50.1"},"reference-count":21,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01KG2005"],"award-info":[{"award-number":["01KG2005"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,7,16]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>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 f\u00fcr 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05360953\">NCT05360953<\/jats:ext-link>\n                      , EudraCT 2021-000319-21.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-098161","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T18:25:39Z","timestamp":1754418339000},"page":"e098161","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Treating nightmares in post-traumatic stress disorder with the \u03b1-adrenergic agents clonidine and doxazosin: protocol for a phase II randomised, double-blind, placebo-controlled parallel-group study (ClonDoTrial)"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct05360953","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05360953","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3165-8684","authenticated-orcid":false,"given":"Stefan","family":"Roepke","sequence":"first","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola","family":"Schoofs","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Campus St. Hedwig Hospital, Department of Psychiatry and Psychotherapy, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathlen","family":"Priebe","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Campus St. Hedwig Hospital, Department of Psychiatry and Psychotherapy, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Wuelfing","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Campus St. Hedwig Hospital, Department of Psychiatry and Psychotherapy, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Roehle","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Institute of Biometry and Clinical Epidemiology, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tolou","family":"Maslahati","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Stieglbauer","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Biedermann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingo","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Gallinat","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Ethofer","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas J","family":"Fallgatter","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Hanewald","sequence":"additional","affiliation":[{"name":"Universitatsklinikum Giessen und Marburg - Standort Marburg, Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Mulert","sequence":"additional","affiliation":[{"name":"Universitatsklinikum Giessen und Marburg - Standort Marburg, Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Schmahl","sequence":"additional","affiliation":[{"name":"Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Otte","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Koglin","sequence":"additional","affiliation":[{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of of Freie Universit\u00e4t Berlin and Humboldt\u2014Universit\u00e4t zu Berlin, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"2025123106452394000_15.8.e098161.1","doi-asserted-by":"publisher","DOI":"10.1097\/NMD.0b013e3182392c0d"},{"key":"2025123106452394000_15.8.e098161.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2007.08.008"},{"key":"2025123106452394000_15.8.e098161.3","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1037\/tra0000254","article-title":"Longitudinal analysis of quality of life across the trauma spectrum","volume":"9","author":"Monson","year":"2017","journal-title":"Psychol Trauma"},{"key":"2025123106452394000_15.8.e098161.4","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv217"},{"key":"2025123106452394000_15.8.e098161.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1612499"},{"key":"2025123106452394000_15.8.e098161.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.06.032"},{"key":"2025123106452394000_15.8.e098161.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2007.09.003"},{"key":"2025123106452394000_15.8.e098161.8","doi-asserted-by":"crossref","unstructured":"Belkin MR , Schwartz TL . Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder. Drugs Context 2015;4. doi:10.7573\/dic.212286","DOI":"10.7573\/dic.212286"},{"key":"2025123106452394000_15.8.e098161.9","doi-asserted-by":"publisher","DOI":"10.1016\/s0278-5846(01)00203-2"},{"key":"2025123106452394000_15.8.e098161.10","doi-asserted-by":"crossref","unstructured":"Singh B , Hughes AJ , Mehta G , et al . Efficacy of Prazosin in Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis. Prim Care Companion CNS Disord 2016;18. doi:10.4088\/PCC.16r01943","DOI":"10.4088\/PCC.16r01943"},{"key":"2025123106452394000_15.8.e098161.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507598"},{"key":"2025123106452394000_15.8.e098161.12","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3390\/jcm5120117","article-title":"Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center","volume":"5","author":"Detweiler","year":"2016","journal-title":"J Clin Med"},{"key":"2025123106452394000_15.8.e098161.13","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e31819a4bae"},{"key":"2025123106452394000_15.8.e098161.14","doi-asserted-by":"crossref","first-page":"e561","DOI":"10.4088\/JCP.14m09681","article-title":"Doxazosin XL Reduces Symptoms of Posttraumatic Stress Disorder in Veterans With PTSD","volume":"77","author":"Rodgman","year":"2016","journal-title":"J Clin Psychiatry"},{"key":"2025123106452394000_15.8.e098161.15","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/JCP.0b013e3181c827ae","article-title":"Doxazosin treatment for posttraumatic stress disorder","volume":"30","author":"De Jong","year":"2010","journal-title":"J Clin Psychopharmacol"},{"key":"2025123106452394000_15.8.e098161.16","first-page":"26","article-title":"Doxazosin, an \u03b1-1-adrenergic-receptor Antagonist, for Nightmares in Patients with Posttraumatic Stress Disorder and\/or Borderline Personality Disorder: a Chart Review","volume":"50","author":"Roepke","year":"2017","journal-title":"Pharmacopsychiatry"},{"key":"2025123106452394000_15.8.e098161.17","doi-asserted-by":"crossref","DOI":"10.4088\/JCP.21m14367","article-title":"A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans","volume":"84","author":"Back","year":"2023","journal-title":"J Clin Psychiatry"},{"key":"2025123106452394000_15.8.e098161.18","doi-asserted-by":"publisher","DOI":"10.2190\/PM.44.2.g"},{"key":"2025123106452394000_15.8.e098161.19","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5461"},{"key":"2025123106452394000_15.8.e098161.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2012.06.001"},{"key":"2025123106452394000_15.8.e098161.21","unstructured":"Buuren S . Chapter 2. multiple imputation. In: Flexible imputation of missing data. Boca Raton: Chapman and Hall\/CRC Press, 2012: 25\u201352."}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-098161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:45:58Z","timestamp":1767192358000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-098161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":21,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,5]]},"published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1136\/bmjopen-2024-098161"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-098161","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]}}}