Repurposing Low-Dose Clonidine for PTSD in Veterans

NCT04877093 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: IRB0010594420-1057
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: Veterans with PTSD prescribed clonidine will demonstrate improvements in PTSD symptoms, including daytime, nighttime, and sleep-related behaviors.

Conditions

PTSD; Posttraumatic Stress Disorder; Sleep

Keywords

PTSD; veterans; military; sleep; adrenergic receptor

Outcome Measures

Primary Outcomes (3)

• Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) at 6 weeks into phase

  Scored 0-21, where higher scores indicate worse sleep quality.

  Week 6 of Current Phase

• Change from Baseline in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) questions B2 and E6 at 6 weeks into phase

  Measures PTSD symptoms on sleep, with each question scored 1-4, where higher scores indicate more severe symptoms.

  Week 6 of Current Phase

• Change from Baseline in PTSD Checklist-Military Version (PCL-5) at 6 weeks into phase

  Includes 20 items with a severity score range 0-80. Includes the ability to treat each item rated as 2 = "Moderately" or higher as a symptom endorsed, which allows following the DSM-5 diagnostic rule which requires at least: 1 Criterion B item (questions 1-5), 1 Criterion C item (questions 6-7), 2 Criterion D items (questions 8-14), 2 Criterion E items (questions 15-20). In general, use of a cutoff score tends to produce more reliable results than the DSM-5 diagnostic rule.

  Week 6 of Current Phase

Secondary Outcomes (3)

• Change from Baseline in Patient Health Questionnaire (PHQ9) at 6 weeks into phase

  Week 6 of Current Phase

• Change from Baseline in Sleep Diary at 6 weeks into phase

  Week 6 of Current Phase

• Change from Baseline in quality of life scale (Q-LES-Q-SF) at 6 weeks into phase

  Week 6 of Current Phase

Study Arms (2)

Clonidine Phase

EXPERIMENTAL

Participants will receive clonidine titrations across 6 weeks. Note that this is a crossover design, so patients will move across phases.

Drug: Clonidine Pill

Placebo Phase

PLACEBO COMPARATOR

Participants will receive placebo titrations across 6 weeks. Note that this is a crossover design, so patients will move across phases.

Other: Placebo

Interventions

Clonidine Pill DRUG

The study will use a flexible-dose adjustment schedule to identify the minimum dose needed to alleviate symptoms while also ensuring acceptable adverse effects. In other words, all subjects will start at the minimum dose (0.1 mg/night). Near the end of every week, each subject will be assessed for symptom alleviation and adverse events by asking the patient two questions from the CAPS-5 (questions B2 and E6. At baseline, each patient will have scored a ≥3 on each of these questions. If one or both scores remain at ≥3 and if any reported adverse events are marked acceptable by both the clinician and subject, then the dosage for the following week will be increased one level according to the titration chart. However, if both scores for these questions are ≤2 and any current adverse events are acceptable, then the dosage will remain the same. Finally, if any adverse events are deemed unacceptable, the clonidine dosage will be reduced to the lowest acceptable daily dosage.

Clonidine Phase

Placebo OTHER

Blinded placebo capsules will be provided to participants.

Placebo Phase

Eligibility Criteria

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

You may qualify if:

• ≥18 years old
• US military veteran
• Currently has PTSD diagnosis as determined by clinical diagnosing or by the PI
• Screening score on PCL5 minimum of 40 (per data from previous studies36-38, a PCL5 score of 40 is roughly equivalent to a CAPS score of 30)
• Scores ≥10 on PCL5 items 1-5 (intrusion) or scores ≥10 on PCL5 items 15-20
• From PCL5 questionnaire, must score the following minimum in each of the following categories:
• x score of 2 on Questions 1-5
• x score of 2 on Questions 6-7
• x score of 2 on Questions 8-14
• x score of 2 on Questions 15-20
• Has score ≥3 on CAPS nightmare items B2 and E6
• Speaks and understands English
• Willing to come into the clinic as programmed

You may not qualify if:

• Pregnant or breastfeeding
• At Moderate or High risk of suicide based on "past month" column of the Columbia-Suicide Severity Rating Scale (CSSR-S) screen version - recent.
• Has acute or unstable mental illness or any cognitive issues which the PI determines would interfere with engagement in the study (e.g., active schizophrenia, uncontrolled bipolar, history of neurocognitive impairment, history of moderate-severe traumatic brain injury)
• Currently receiving exposure therapy
• Urgent hypertension (BP above 160/100) or symptomatic of hypertension (having a hypertensive emergency)
• Blood pressure under 100/60 or symptoms of low blood pressure (light headedness, dizziness, heart palpitations, or other symptoms as determined by clinician).
• Any contraindications to taking clonidine such as:
• Known hypersensitivity to clonidine
• History of 2nd or 3rd degree atrioventricular block
• History of sinus bradycardia
• History of pheochromocytoma
• History of Raynaud's phenomenon
• Stage 5 Kidney disease
• Recent myocardial infarction (\<6 months)
• History of cerebrovascular disease or recent stoke (\<6 months)

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Aurora Psychiatric Hospital

Wauwatosa, Wisconsin, 53213, United States

RECRUITING

Related Publications (3)

• Kang HK, Bullman TA. Risk of suicide among US veterans after returning from the Iraq or Afghanistan war zones. JAMA. 2008 Aug 13;300(6):652-3. doi: 10.1001/jama.300.6.652. No abstract available.

  PMID: 18698062 BACKGROUND

• Buchholz KR, Bohnert KM, Sripada RK, Rauch SA, Epstein-Ngo QM, Chermack ST. Associations between PTSD and intimate partner and non-partner aggression among substance using veterans in specialty mental health. Addict Behav. 2017 Jan;64:194-199. doi: 10.1016/j.addbeh.2016.08.039. Epub 2016 Aug 31.

  PMID: 27636157 BACKGROUND

• Norman SB, Haller M, Hamblen JL, Southwick SM, Pietrzak RH. The burden of co-occurring alcohol use disorder and PTSD in U.S. Military veterans: Comorbidities, functioning, and suicidality. Psychol Addict Behav. 2018 Mar;32(2):224-229. doi: 10.1037/adb0000348.

  PMID: 29553778 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Clonidine

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

Study Officials

• Gregory Burek, MD, MS

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

• Michael Fendrich, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin Petranu

CONTACT

414-219-2000; kevin.petranu@aah.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacist will determine the groups for each patient and will not reveal groups to anyone on the study team or the participant until they have finished the trial.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, blinded crossover

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: May 7, 2021
• Study Start: June 1, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (1)