Treating Nightmares in Posttraumatic Stress Disorder With Clonidine and Doxazosin

NCT05360953 | Suspended Phase 2 DMC

• 1 other identifier: ClonDO
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 5

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.

Conditions

Posttraumatic Stress Disorder

Keywords

Nightmares; Posttraumatic Stress Disorder; Clonidine; Doxazosin

Outcome Measures

Primary Outcomes (1)

• Change of frequency and intensity of nightmares

  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.

  10 weeks

Secondary Outcomes (19)

• Change of frequency and intensity of nightmares

  1,2,3,4,5,6 and 8 weeks

• 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 Pittsburgh Sleep Quality Index-Addendum for PTSD

  6 and 10 weeks

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

  6 and 10 weeks

• Weekly mean of change from baseline of daily total sleep time

  during 10 weeks

Study Arms (3)

Arm Clonidine

EXPERIMENTAL

Drug: Clonidine

Arm Doxazosin

EXPERIMENTAL

Drug: Doxazosin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Clonidine DRUG

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.

Arm Clonidine

Doxazosin DRUG

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.

Arm Doxazosin

Placebo DRUG

All patients enrolled establish their individually tolerable dose by dose Titration. Dosage up to a maximum of 5 capsules. Using capsules of placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of posttraumatic stress disorder (PTSD) according to DSM 5 with a 20 item CAPS-5 total score ≥ 26
• At least two nightmares a week, an intensity score ≥ 2, with a CAPS-IV B2 (frequency and intensity for the last week) score ≥ 5
• Men and women between 18 and 65 years of age
• Written informed consent
• 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)
• The patient is not breastfeeding
• Women of child-bearing potential must have a negative urine or serum pregnancy test
• All participants must use highly effective contraception
• 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).

You may not qualify if:

• Disturbances of cardiac impulse formation and conduction, for example sick sinus syndrome or atrioventricular block second and third degree
• Bradycardia, with a heart rate less than 50 beats per minute
• Current major depressive episode and a MADRS score \> 34
• The patient does have a known allergy, hypersensitivity or contraindication against clonidine, doxazosin, or other types of quinazolines
• History of severe orthostatic hypotension
• Benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary tract infection or bladder stones, hypotension (for benign prostate hyperplasia only)
• Either overflow bladder or anuria with or without progressive renal insufficiency
• Planned cataract surgery (risk of 'Intraoperative Floppy Iris Syndrome')
• Intake of phosphodiesterase-5-inhibitors
• Intake of methylphenidate
• Severe hepatic impairment (ASAT or ALAT greater than two times normal)
• Acute or unstable medical illness
• Known HIV- and/or active Hepatitis-B- or Hepatitis-C-infection
• Current or past malignant illness
• The patient does have clinically significant abnormalities in 12-lead ECG

Sponsors & Collaborators

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

Study Sites (5)

Universitätsklinikum Tübingen

Tübingen, Germany, 72076, Germany

Location

Berlin St. Hedwig

Berlin, 10115, Germany

Location

Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Psychiatrie und Psychotherapie

Berlin, 12203, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Zentralinstitut für Seelische Gesundheit Mannheim

Mannheim, 86159, Germany

Location

Related Publications (1)

• Roepke S, Schoofs N, Priebe K, Wuelfing F, Roehle R, Maslahati T, Stieglbauer K, Biedermann S, Schaefer I, Gallinat J, Ethofer T, Fallgatter AJ, Hanewald B, Mulert C, Schmahl C, Otte C, Koglin S. Treating nightmares in post-traumatic stress disorder with the alpha-adrenergic agents clonidine and doxazosin: protocol for a phase II randomised, double-blind, placebo-controlled parallel-group study (ClonDoTrial). BMJ Open. 2025 Aug 5;15(8):e098161. doi: 10.1136/bmjopen-2024-098161.

  PMID: 40764082 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Clonidine; Doxazosin

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Prazosin; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stefan Roepke, MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Stefan Roepke, MD

Model Details: Randomized controlled study (double-blind)

Study Record Dates

• First Submitted: April 29, 2022
• First Posted: May 4, 2022
• Study Start: June 17, 2022
• Primary Completion: August 8, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: August 13, 2025

Record last verified: 2025-01

Locations

DE (5)