Clinical trial NCT05360953: Treating Nightmares in Posttraumatic Stress Disorder with Clonidine and Doxazosin
Official title: Treating Nightmares in Posttraumatic Stress Disorder with the Α-adrenergic Agents Clonidine and Doxazosin: a Randomized-Controlled Feasibility Study (ClonDoTrial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Posttraumatic Stress Disorder
Keywords: Nightmares
Posttraumatic Stress Disorder
Clonidine
Doxazosin
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
First posted: 2022-05-04
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled study (double-blind)
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change of frequency and intensity of nightmares
timeFrame: 10 weeks
Secondary outcomes:
measure: Change of frequency and intensity of nightmares
timeFrame: 1,2,3,4,5,6 and 8 weeks
measure: Change from baseline of the CLINICIAN-ADMINISTERED PTSD SCALE FOR DSM-5 (CAPS-5) total score
timeFrame: 6 and 10 weeks
measure: Change from baseline of the Pittsburgh Sleep Quality Index-Addendum for PTSD
timeFrame: 6 and 10 weeks
measure: Change from baseline of the -Montgomery Asberg Depression Rating Scale (MDRS)
timeFrame: 6 and 10 weeks
measure: Weekly mean of change from baseline of daily total sleep time
timeFrame: during 10 weeks
measure: Weekly mean of change from baseline of the patients sleep onset latency at night (in minutes), assessed with sleep diaries
timeFrame: during 10 weeks
measure: Weekly mean of change from baseline of the patients recuperation of night sleep
timeFrame: during 10 weeks
measure: Weekly mean of change from baseline of the patients time awake at night
timeFrame: during 10 weeks
measure: Weekly mean of change from baseline of the patients number of nightmares last night
timeFrame: during 10 weeks
measure: Weekly mean of change from baseline of the patients intensity of nightmares
timeFrame: during 10 weeks
measure: Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5
timeFrame: 6 and 10 weeks
measure: Change from baseline of the Borderline Symptom List 23 (BSL-23)
timeFrame: 6 and 10 weeks
measure: Change from baseline of the Health-Related Quality of Life (EQ-5D)
timeFrame: 6 and 10 weeks
measure: Overall patients status measured by the Patient Global Impression of Change (PGIC)
timeFrame: 6 and 10 weeks
measure: Change from baseline of the Social and Occupational Functioning Assessment Scale
timeFrame: 6 and 10 weeks
measure: Change from baseline of the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 6 and 10 weeks
measure: Change from baseline of symptoms of PTSD and complex PTSD according to ICD-11 assessed with the International Trauma Questionnaire (ITQ)
timeFrame: 6 and 10 weeks
measure: Responder analysis: proportion of patients showing improvement in nightmares
timeFrame: 10 weeks
measure: Remitter analysis: proportion of patients showing full remission of nightmares
timeFrame: 10 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Berlin St. Hedwig
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Psychiatrie und Psychotherapie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Mannheim
country: Germany
facility: Zentralinstitut für Seelische Gesundheit Mannheim
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
Study officials:
affiliation: Charite University, Berlin, Germany
name: Stefan Roepke, MD
role: PRINCIPAL_INVESTIGATOR
References: