Treating Nightmares in Posttraumatic Stress Disorder With Clonidine and Doxazosin

Posttraumatic Stress Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05360953
• Other study ID #: ClonDo-PTSD
• Status: Recruiting
• Phase: Phase 2
• Start date: April 6, 2022
• Est. completion date: April 1, 2025

Study information

• Verified date: April 2022
• Source: Charite University, Berlin, Germany
• Contact: Stefan Roepke, MD
• Phone: 004930450517545
• Email: stefan.roepke[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 189
• Est. completion date: April 1, 2025
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Disease
• Posttraumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

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.
• 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.
• Placebo
All patients enrolled establish their individually tolerable dose by dose Titration. Dosage up to a maximum of 5 capsules. Using capsules of placebo.

Locations

Country	Name	City	State
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

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change from baseline of the CAPS-5 total score	Change from baseline of the CAPS-5 total score (overall PTSD symptoms, last week)	6 and 10 weeks
Secondary	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)	6 and 10 weeks
Secondary	Change from baseline of the -Montgomery Asberg Depression Rating Scale	Change from baseline of the -Montgomery Asberg Depression Rating Scale (MADRS)	6 and 10 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5	Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5 (PCL-5)	6 and 10 weeks
Secondary	Change from baseline of the Borderline Symptom List 23	Change from baseline of the Borderline Symptom List 23 (BSL-23) score	6 and 10 weeks
Secondary	Change from baseline of the Health-Related Quality of Life	Change from baseline of the Health-Related Quality of Life (EQ-5D) score	6 and 10 weeks
Secondary	Overall patients status measured by the Patient Global Impression of Change	Overall patients status measured by the Patient Global Impression of Change (PGIC)	6 and 10 weeks
Secondary	Change from baseline of the Social and Occupational Functioning Assessment Scale	Change from baseline of the Social and Occupational Functioning Assessment Scale (SOFAS)	6 and 10 weeks
Secondary	Change from baseline of the Pittsburgh Sleep Quality Index	Change from baseline of the Pittsburgh Sleep Quality Index (PSQI)	6 and 10 weeks
Secondary	Change from baseline of symptoms of PTSD and complex PTSD according to ICD-11 assessed with the International Trauma Questionnaire	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
Secondary	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 CAPS-IV B2 =50% assessed at the end of treatment	10 weeks
Secondary	Remitter analysis: proportion of patients showing full remission of nightmares	Remitter analysis: proportion of patients showing full remission of nightmares defined as CAPS-IV B2 = 0, assessed at the end of treatment	10 weeks