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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

6 Apr 2022 → 8 Aug 2025

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Federal Ministry of Education and Research (BMBF)

External identifiers

EU CT number

2024-517537-40-00

EudraCT number

2021-000319-21

WHO UTN

U1111-1312-7144

ClinicalTrials.gov

NCT05360953

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To examine whether oral clonidine (0.075-0.375 mg) or doxazosin (1-10 mg) reduces nightmares to a greater extent than placebo in patients with posttraumatic stress disorder.

Secondary objectives 1

1. Secondary objectives of the study are to examine the efficacy of oral clonidine or doxazosin in reducing other PTSD-specific symptoms, general sleep parameters and depressive symptoms in patients with posttraumatic stress disorder.

Conditions and MedDRA coding

Posttraumatic Stress Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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 CAPSIV 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 30

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary efficacy endpoint: 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 (10 weeks, visit 9). A lower score indicates less frequent and/or intense nightmares.

Secondary endpoints 14

1. Change from baseline of the frequency and intensity of nightmares, measured with the Clinician-Administered PTSD Scale-IV (CAPS-IV) B2 score for the last week, range 0–8, at Visit 2 – Visit 8
2. Change from baseline of the CAPS-5 total score (overall PTSD symptoms, last week) at Visit 7 and Visit 9
3. Change from baseline of the Pittsburgh Sleep Quality Index- Addendum for PTSD (PSQI A) (PTSD related sleep symptoms) at Visit 7 and Visit 9
4. Change from baseline of the Montgomery Asberg Depression Inventory (MADRS) at Visit 7 and Visit 9
5. Weekly mean of change from baseline of the patients daily total sleep time (in minutes), sleep onset latency at night (in minutes), recuperation of night sleep (5-point Likert scale, 1 = very much; 5 = not at all), and time awake at night (in minutes), number of nightmares last night (0, 1, 3, 4 or more) and intensity of nightmares (5-point Likert scale, 0 = not at all; 5 = extreme) assessed with sleep diaries during Visit 2 – Visit 9
6. Change from baseline of PTSD symptoms assessed with the PTSD Checklist for DSM-5 (PCL-5) at Visit 7 and Visit 9
7. Change from baseline of the Borderline Symptom List 23 (BSL-23) score at Visit 7 and Visit 9
8. Change from baseline of the Health-Related Quality of Life (EQ-5D) score at Visit 7 and Visit 9
9. Overall patient status measured by the Patient Global Impression of Change (PGIC) at Visit 7 and Visit 9
10. Change from baseline of the Social and Occupational Functioning Assessment Scale (SOFAS) at Visit 7 and Visit 9
11. Change from baseline of the Pittsburgh Sleep Quality Index (PSQI) at Visit 7 and Visit 9
12. Change from baseline of symptoms of PTSD and complex PTSD according to ICD-11 assessed with the International Trauma Questionnaire (ITQ) at Visit 7 and Visit 9
13. 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 (Visit 9)
14. Remitter analysis: proportion of patients showing full remission of nightmares defined as CAPS-IV B2 = 0, assessed at the end of treatment (Visit 9)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Hindenburgdamm 30, Lichterfelde Lichterfelde

City

Berlin

Postcode

12203

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Prof.Dr. Stefan Röpke

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Dr. Stefanie Koglin

Third parties 8

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications