Treating Nightmares in Posttraumatic Stress Disorder With Clonidine and Doxazosin

Treating Nightmares in Posttraumatic Stress Disorder With the α-adrenergic Agents Clonidine and Doxazosin: A Randomized-Controlled Feasibility Study (ClonDoTrial)

This randomized controlled trial will test the hypothesis that oral Clonidine or Doxazosin improves nightmares (primary outcome), other PTSD symptoms and psychopathology (secondary outcomes) to a greater extent than placebo over a ten week intervention phase in a parallel group design.

Study Overview

• Status: Suspended
• Conditions: Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: Clonidine; Drug: Doxazosin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10115
    • Berlin St. Hedwig
  • Berlin, Germany, 12203
    • Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Psychiatrie und Psychotherapie
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Mannheim, Germany, 86159
    • Zentralinstitut für Seelische Gesundheit Mannheim
  • Tübingen, Germany, 72076
    • Universitatsklinikum Tubingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of posttraumatic stress disorder (PTSD) according to DSM 5 with a 20 item CAPS-5 total score ≥ 26
2. At least two nightmares a week, an intensity score ≥ 2, with a CAPS-IV B2 (frequency and intensity for the last week) score ≥ 5
3. Men and women between 18 and 65 years of age
4. Written informed consent
5. The patient has the capacity to give consent (He/she is able to understand the nature and anticipated effects/side effects of the proposed medical intervention)
6. The patient is not breastfeeding
7. Women of child-bearing potential must have a negative urine or serum pregnancy test
8. All participants must use highly effective contraception
9. The patient received stable pharmacological medication for at least 4 weeks or at least five times the value of a elimination half-life prior to study baseline (any changes in medication dose or frequency of therapy must be answered with no).

Exclusion Criteria:

1. Disturbances of cardiac impulse formation and conduction, for example sick sinus syndrome or atrioventricular block second and third degree
2. Bradycardia, with a heart rate less than 50 beats per minute
3. Current major depressive episode and a MADRS score > 34
4. The patient does have a known allergy, hypersensitivity or contraindication against clonidine, doxazosin, or other types of quinazolines
5. History of severe orthostatic hypotension
6. Benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary tract infection or bladder stones, hypotension (for benign prostate hyperplasia only)
7. Either overflow bladder or anuria with or without progressive renal insufficiency
8. Planned cataract surgery (risk of 'Intraoperative Floppy Iris Syndrome')
9. Intake of phosphodiesterase-5-inhibitors
10. Intake of methylphenidate
11. Severe hepatic impairment (ASAT or ALAT greater than two times normal)
12. Acute or unstable medical illness
13. Known HIV- and/or active Hepatitis-B- or Hepatitis-C-infection
14. Current or past malignant illness
15. The patient does have clinically significant abnormalities in 12-lead ECG
16. The patient does have clinically significant laboratory abnormalities
17. Epilepsy
18. Dementia
19. Current substance/alcohol use disorder (≤ 3 months)
20. Psychotic disorder
21. Bipolar disorder
22. Current anorexia nervosa
23. Acute suicidality (any suicidal ideation of type of 5 in the C-SSRS in the past month)
24. Intake of alpha adrenergic agents (Clonidine, doxazosin, or others) within 4 weeks prior to baseline (randomization)
25. Trauma-focused psychotherapy four weeks before the trial
26. Initiation of sleep medication 4 weeks prior to baseline
27. The patient is unwilling to consent to saving, processing and propagation of pseudonymized medical data for study reasons
28. Patients, who may be dependent on the sponsor, the investigator or the trial sites
29. The patient is legally detained in an official institution
30. The patient did participated in other interventional trials during the 3 months before and at the time of this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; All patients enrolled establish their individually tolerable dose by dose Titration. Dosage up to a maximum of 5 capsules. Using capsules of placebo.
Experimental: Arm Clonidine	Drug: Clonidine; All patients enrolled establish their individually tolerable dose by dose Titration. Dosage up to a maximum of 0.375 clonidine. Using capsules of 0,075 mg clonidine.
Experimental: Arm Doxazosin	Drug: Doxazosin; All patients enrolled establish their individually tolerable dose by dose. Dosage up to a maximum of 10 mg doxazosin. Using capsules of 2 mg doxazosin. Titration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of frequency and intensity of nightmares	Change of Frequency and intensity of nightmares, measured with the Clinician-Administered PTSD Scale-IV (CAPS-IV) B2 score for the last week, range 0-8, from baseline until directly after last intervention. A lower score indicates less frequent and/or intense nightmares.	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly mean of change from baseline of daily total sleep time	Weekly mean of change from baseline of the patients daily total sleep time (in minutes), assessed with sleep diaries	during 10 weeks
Weekly mean of change from baseline of the patients time awake at night	Weekly mean of change from baseline of the patients time awake at night (in minutes), assessed with sleep diaries	during 10 weeks
Weekly mean of change from baseline of the patients number of nightmares last night	Weekly mean of change from baseline of the patients number of nightmares last night (0, 1, 3, 4 or more) assessed with sleep diaries	during 10 weeks
Weekly mean of change from baseline of the patients intensity of nightmares	Weekly mean of change from baseline of the patients intensity of nightmares (5-point Likert scale, 0 = not at all; 5 = extreme) assessed with sleep diaries	during 10 weeks
Change of frequency and intensity of nightmares	Change of Frequency and intensity of nightmares, measured with the Clinician-Administered PTSD Scale-IV (CAPS-IV) B2 score for the last week, range 0-8, from baseline until directly after last intervention. A lower score indicates less frequent and/or intense nightmares.	1,2,3,4,5,6 and 8 weeks
Weekly mean of change from baseline of the patients sleep onset latency at night (in minutes), assessed with sleep diaries	Weekly mean of change from baseline of the patients sleep onset latency at night (in minutes), assessed with sleep diaries	during 10 weeks
Weekly mean of change from baseline of the patients recuperation of night sleep	Weekly mean of change from baseline of the patients recuperation of night sleep (5-point Likert scale, 1 = very much; 5 = not at all), assessed with sleep diaries	during 10 weeks
Change from baseline of the CLINICIAN-ADMINISTERED PTSD SCALE FOR DSM-5 (CAPS-5) total score	Change from baseline of the CAPS-5 total score (overall PTSD symptoms, last week) (minimum value = 0; maximum value = 80; higher scores indicate higher PTSD symptom severity)	6 and 10 weeks
Change from baseline of the Pittsburgh Sleep Quality Index-Addendum for PTSD	Change from baseline of the Pittsburgh Sleep Quality Index-Addendum for PTSD (PSQI A) (PTSD related sleep symptoms); (score = 0-21 point, 0 = no difficulty; 21 = severe difficulty in all areas)	6 and 10 weeks
Change from baseline of the -Montgomery Asberg Depression Rating Scale (MDRS)	Change from baseline of the MADRS (scores: 0 - 60; 0 - 6 = no depression; 7 - 19 = light depression; 20 - 34 = moderate depression; > 34 severe depression)	6 and 10 weeks
Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5	Change from baseline of PCL-5 PTSD Checklist for DSM-5; Score can range from 0-80 (higher scores indicate a higher PTSD symptom severity) Score (0 - 80; higher scores indicating higher chance of a possible PTSD diagnosis)	6 and 10 weeks
Change from baseline of the Borderline Symptom List 23 (BSL-23)	Change from baseline of the BSL-23 score (Scores can range from 0 to 92; higher scores indicate higher Borderline symptom severity) Scores: 0 - 4 (0 = no Borderline Symptoms; 4 = severe borderline symptoms)	6 and 10 weeks
Change from baseline of the Health-Related Quality of Life (EQ-5D)	Change from baseline of the EQ-5D score (score can range from 0-100; with higher scores indicating a better Health Related Quality of Life) Scores = 1-5 (1 = no problems; 5 = extreme problems)	6 and 10 weeks
Overall patients status measured by the Patient Global Impression of Change (PGIC)	Overall patients status measured by the PGIC (Scores can range from 0 - 7; with higher scores indicating higher improvement) score: 0 - 7 (0 = disease deterioration; 7 = disease improvement)	6 and 10 weeks
Change from baseline of the Social and Occupational Functioning Assessment Scale	Change from baseline of the Social and Occupational Functioning Assessment Scale (SOFAS); Scores can range from 1 - 100, with higher scores indicating better social and occupational functioning	6 and 10 weeks
Change from baseline of the Pittsburgh Sleep Quality Index (PSQI)	Change from baseline of the PSQI; Scores can range from 0 to 21, with higher scores indicating lower sleep quality Scores : 0 - 21, lower scores denote a healthier sleep quality	6 and 10 weeks
Change from baseline of symptoms of PTSD and complex PTSD according to ICD-11 assessed with the International Trauma Questionnaire (ITQ)	Change from baseline of symptoms of ITQ, dimensional scores can range from 0 - 24, with higher scores indicating highter PTSD symptom severity Categorical Scoring: For PTSD items, endorsement of a symptom or functional impairment item is defined as a score of 2 or greater. The diagnosis of PTSD is indicated based on the following criteria: Question 1 or 2 = one or more items endorsed (re-experiencing); Question 3 or 4 = one or more items endorsed (avoidance); Question 5 or 6 = one or more items endorsed (sense of current threat); Question 7, 8 or 9 = one or more items endorsed (PTSD functional impairment)	6 and 10 weeks
Responder analysis: proportion of patients showing improvement in nightmares	Responder analysis: proportion of patients showing improvement in nightmares (change from baseline) defined as decrease of CLINICIAN-ADMINISTERED PTSD SCALE FOR DSM-IV (CAPS-IV B2) ≥50% assessed at the end of treatment Score: 0 - 8 (higher scores indicate higher frequency and severity of nightmares)	10 weeks
Remitter analysis: proportion of patients showing full remission of nightmares	Remitter analysis: proportion of patients showing full remission of nightmares defined as CLINICIAN-ADMINISTERED PTSD SCALE FOR DSM-IV (CAPS-IV B2) = 0, assessed at the end of treatment; 0 = no nightmares (score 0 - 8; higher scores indicate higher frequency and severity of nightmares))	10 weeks

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Principal Investigator: Stefan Roepke, MD, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2022
• Primary Completion (Actual): August 8, 2025
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Posttraumatic Stress Disorder; Nightmares; Clonidine; Doxazosin
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Analgesics; Neurotransmitter Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Antihypertensive Agents; Sympatholytics; Adrenergic Antagonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Clonidine; Doxazosin
• Other Study ID Numbers: ClonDO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No