Using Clonidine and Doxazosin to Treat Nightmares in PTSD

Treating Nightmares in Posttraumatic Stress Disorder with the Α-adrenergic Agents Clonidine and Doxazosin: a Randomized-Controlled Feasibility Study (ClonDoTrial)

This study is testing if the medications Clonidine and Doxazosin can help people with PTSD have fewer and less intense nightmares.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 189 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Charite University, Berlin, Germany (Academic / other)
• Locations: 5 sites (Berlin and 4 other locations)
• Trial ID: NCT05360953 on ClinicalTrials.gov

What this trial studies

This randomized controlled trial aims to evaluate the effectiveness of oral Clonidine and Doxazosin in reducing nightmares among individuals diagnosed with posttraumatic stress disorder (PTSD). Participants will be randomly assigned to receive either the medications or a placebo over a ten-week period. The primary outcome will focus on the frequency and intensity of nightmares, while secondary outcomes will assess other PTSD symptoms and overall psychopathology. The study will include both men and women aged 18 to 65 who meet specific eligibility criteria related to their PTSD diagnosis and nightmare frequency.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 65 with a diagnosis of PTSD who experience at least two nightmares per week.

Not a fit: Patients who do not experience frequent nightmares or have significant cardiac impulse formation disturbances may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for alleviating nightmares in patients with PTSD, potentially improving their overall quality of life.

How similar studies have performed: While there have been studies on PTSD treatments, the specific combination of Clonidine and Doxazosin for nightmares is relatively novel and has not been extensively tested.

Eligibility criteria

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

Where this trial is running

Berlin and 4 other locations

• Berlin St. Hedwig — Berlin, Germany (Recruiting)
• Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Psychiatrie und Psychotherapie — Berlin, Germany (Recruiting)
• Universitätsklinikum Hamburg-Eppendorf — Hamburg, Germany (Recruiting)
• Zentralinstitut für Seelische Gesundheit Mannheim — Mannheim, Germany (Recruiting)
• Universitätsklinikum Tübingen — Tübingen, Germany (Recruiting)

Study contacts

• Principal investigator: Stefan Roepke, MD — Charite University, Berlin, Germany
• Study coordinator: Stefan Roepke, MD

Conditions Posttraumatic Stress Disorder; Nightmares; Clonidine; Doxazosin