Treating Nightmares in Posttraumatic Stress Disorder With Clonidine and Doxazosin

• Sponsor: Charite University, Berlin, Germany (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05360953
• Collaborator: German Federal Ministry of Education and Research (Other)
• Enrollment: 189
• Locations: 4
• Arms: 3
• Anticipated Duration (Months): 35.8
• Patients Per Site: 47.3
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Posttraumatic Stress Disorder	Drug: Clonidine; Drug: Doxazosin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized controlled study (double-blind)Randomized controlled study (double-blind)
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treating Nightmares in Posttraumatic Stress Disorder With the α-adrenergic Agents Clonidine and Doxazosin: A Randomized-Controlled Feasibility Study (ClonDoTrial)
• Actual Study Start Date: Apr 6, 2022
• Anticipated Primary Completion Date: Jul 31, 2024
• Anticipated Study Completion Date: Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
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.
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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. Change from baseline of the CAPS-5 total score [6 and 10 weeks]

   Change from baseline of the CAPS-5 total score (overall PTSD symptoms, last week)

3. 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)

4. Change from baseline of the -Montgomery Asberg Depression Rating Scale [6 and 10 weeks]

   Change from baseline of the -Montgomery Asberg Depression Rating Scale (MADRS)

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5 [6 and 10 weeks]

    Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5 (PCL-5)

12. Change from baseline of the Borderline Symptom List 23 [6 and 10 weeks]

    Change from baseline of the Borderline Symptom List 23 (BSL-23) score

13. Change from baseline of the Health-Related Quality of Life [6 and 10 weeks]

    Change from baseline of the Health-Related Quality of Life (EQ-5D) score

14. Overall patients status measured by the Patient Global Impression of Change [6 and 10 weeks]

    Overall patients status measured by the Patient Global Impression of Change (PGIC)

15. 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)

16. Change from baseline of the Pittsburgh Sleep Quality Index [6 and 10 weeks]

    Change from baseline of the Pittsburgh Sleep Quality Index (PSQI)

17. Change from baseline of symptoms of PTSD and complex PTSD according to ICD-11 assessed with the International Trauma Questionnaire [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)

18. 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 CAPS-IV B2 ≥50% assessed at the end of treatment

19. Remitter analysis: proportion of patients showing full remission of nightmares [10 weeks]

    Remitter analysis: proportion of patients showing full remission of nightmares defined as CAPS-IV B2 = 0, assessed at the end of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Berlin St. Hedwig	Berlin		Germany	10115
2	Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Psychiatrie und Psychotherapie	Berlin		Germany	12203
3	Universitätsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
4	Zentralinstitut für Seelische Gesundheit Mannheim	Mannheim		Germany	86159

Sponsors and Collaborators

• Charite University, Berlin, Germany
• German Federal Ministry of Education and Research

Investigators

• Principal Investigator: Stefan Roepke, MD, Charite University, Berlin, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Stefan Roepke, Prof. Dr. Stefan Roepke, MD, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT05360953
• Other Study ID Numbers: ClonDo-PTSD
• First Posted: May 4, 2022
• Last Update Posted: May 4, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Stefan Roepke, Prof. Dr. Stefan Roepke, MD, Charite University, Berlin, Germany: Nightmares; Posttraumatic Stress Disorder; Clonidine; Doxazosin
• Additional relevant MeSH terms: Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Clonidine; Doxazosin

Study Results

No Results Posted as of May 4, 2022