Treating Nightmares in Posttraumatic Stress Disorder with Clonidine and Doxazosin

Phase 2

Recruiting

• Conditions: Posttraumatic Stress Disorder
• Interventions: Drug: Clonidine; Drug: Doxazosin; Drug: Placebo

• Registration Number: NCT05360953
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-29
• Study First Submitted QC: 2022-04-29
• Study First Posted: 2022-05-04
• Study Start: 2022-06-17
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-06
• Last Update Posted: 2025-01-07
• Primary Completion: 2026-02-28
• Study Completion: 2026-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 189

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm Clonidine	Clonidine	-
Arm Doxazosin	Doxazosin	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change of frequency and intensity of nightmares	10 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change of frequency and intensity of nightmares	1,2,3,4,5,6 and 8 weeks	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.
Change from baseline of the CLINICIAN-ADMINISTERED PTSD SCALE FOR DSM-5 (CAPS-5) total score	6 and 10 weeks	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)
Change from baseline of the Pittsburgh Sleep Quality Index-Addendum for PTSD	6 and 10 weeks	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)
Change from baseline of the -Montgomery Asberg Depression Rating Scale (MDRS)	6 and 10 weeks	Change from baseline of the MADRS (scores: 0 - 60; 0 - 6 = no depression; 7 - 19 = light depression; 20 - 34 = moderate depression; \> 34 severe depression)
Weekly mean of change from baseline of daily total sleep time	during 10 weeks	Weekly mean of change from baseline of the patients daily total sleep time (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 sleep onset latency at night (in minutes), assessed with sleep diaries
Weekly mean of change from baseline of the patients recuperation of night sleep	during 10 weeks	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
Weekly mean of change from baseline of the patients time awake at night	during 10 weeks	Weekly mean of change from baseline of the patients time awake at night (in minutes), assessed with sleep diaries
Weekly mean of change from baseline of the patients number of nightmares last night	during 10 weeks	Weekly mean of change from baseline of the patients number of nightmares last night (0, 1, 3, 4 or more) assessed with sleep diaries
Weekly mean of change from baseline of the patients intensity of nightmares	during 10 weeks	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
Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5	6 and 10 weeks	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)
Change from baseline of the Borderline Symptom List 23 (BSL-23)	6 and 10 weeks	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)
Change from baseline of the Health-Related Quality of Life (EQ-5D)	6 and 10 weeks	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)
Overall patients status measured by the Patient Global Impression of Change (PGIC)	6 and 10 weeks	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)
Change from baseline of the Social and Occupational Functioning Assessment Scale	6 and 10 weeks	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
Change from baseline of the Pittsburgh Sleep Quality Index (PSQI)	6 and 10 weeks	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
Change from baseline of symptoms of PTSD and complex PTSD according to ICD-11 assessed with the International Trauma Questionnaire (ITQ)	6 and 10 weeks	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)
Responder analysis: proportion of patients showing improvement in nightmares	10 weeks	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)
Remitter analysis: proportion of patients showing full remission of nightmares	10 weeks	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))

Trial Locations

Locations (5)

Universitätsklinikum Tübingen; 🇩🇪 Tübingen, Germany

Berlin St. Hedwig; 🇩🇪 Berlin, Germany

Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Psychiatrie und Psychotherapie; 🇩🇪 Berlin, Germany

Universitätsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Zentralinstitut für Seelische Gesundheit Mannheim; 🇩🇪 Mannheim, Germany