Posttraumatic Stress Disorder
Conditions
Keywords
Nightmares, Posttraumatic Stress Disorder, Clonidine, Doxazosin
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.
Interventions
DRUGClonidine
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.
DRUGDoxazosin
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.
DRUGPlacebo
All patients enrolled establish their individually tolerable dose by dose Titration. Dosage up to a maximum of 5 capsules. Using capsules of placebo.
Sponsors
German Federal Ministry of Education and Research
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized controlled study (double-blind)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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)) |
| 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) |
Countries
Germany
Outcome results
None listed