Recruiting
Phase 3

Clonidine

Sponsor:

Wake Forest University Health Sciences

Code:

NCT04877093

Conditions

PTSD

Posttraumatic Stress Disorder

Sleep

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Clonidine Pill

Placebo

Study Details

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

Study ID

NCT04877093

Start date

Jun 1, 2023

Status verified date

Mar, 2026

Completion date

Mar 31, 2027

Anticipated

Primary completion date

Mar 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • ≥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:

  • 1x score of 2 on Questions 1-5
  • 1x score of 2 on Questions 6-7
  • 2x score of 2 on Questions 8-14
  • 2x 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

Exclusion Criteria:

  • 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
  • Recently enrolled (<1 month) in other behavioral health therapies (exclusions made at the PI's discretion depending on therapy type and length since admission)
  • 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)
  • Have used any of the following drugs in the past 30 days, unprescribed or not used as prescribed:

  • Heroin
  • Other opiates/analgesics
  • Barbiturates
  • Other sedatives/, hypnotics, or tranquilizers
  • Cocaine
  • Amphetamines
  • Cannabis
  • Hallucinogens
  • Inhalants
  • Currently have any of the following diagnoses:

  • Opioid use disorder
  • Cocaine use disorder
  • Alcohol use disorder
  • Cannabis use disorder
  • Sleep apnea diagnosis with verbal indication of non-adherence to treatment
  • Were prescribed clonidine within the last 6 months

  • Any α2 agonist

  • Catapres/Kapvay (clonidine)
  • Aldomet (Methyldopa)
  • Zanaflex (Tizanidine)
  • Intuniv (Guanfacine)
  • Lucemyra (Lofexidine)
  • Any α1-adrenergic antagonist

  • Prazosin
  • Terazosin
  • Doxazosin
  • Silodosin
  • Alfuzosin
  • Tamsulosin
  • Any opiate (e.g., buprenorphine, hydrocodone, oxycodone)
  • Any antipsychotic medication

  • Haldol (haloperidol)
  • Loxitane (loxapine)
  • Mellaril (thioridazine)
  • Moban (molindone)
  • Navane (thiothixene)
  • Prolixin (fluphenazine)
  • Serentil (mesoridazine)
  • Stelazine (trifluoperazine)
  • Trilafon (perphenazine)
  • Thorazine (chlorpromazine)
  • Abilify (aripiprazole)
  • Clozaril (clozapine)
  • Geodon (ziprasidone)
  • Risperdal (risperidone)
  • Seroquel (quetiapine)
  • Zyprexa (olanzapine)
  • Benzodiazepines
  • Cyproheptadine
  • Based on PI or study team assessment is cognitively unable to engage in the study
  • Has a legal guardian

Study Design

Enrollment

32 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Clonidine Phase

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

placebo comparator: Placebo Phase

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

Interventions

Clonidine Pill

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.

Placebo

Blinded placebo capsules will be provided to participants.

Primary outcome measure

  • Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) at 6 weeks into phase [ Time Frame: 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 [ Time Frame: Week 6 of Current Phase ]
  • Change from Baseline in PTSD Checklist-Military Version (PCL-5) at 6 weeks into phase [ Time Frame: Week 6 of Current Phase ]

Central Contacts and Locations

Central contacts

Kevin Petranu

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

Locations

Aurora Psychiatric Hospital

Recruiting

Wauwatosa, Wisconsin, United States, 53213

Contacts

Michael Fendrich, PhD

michael.fendrich@aah.org

Principal Investigator:

Gregory A Burek, MD, MS

More Information

Sponsor

Wake Forest University Health Sciences

Last update posted

Mar 31, 2026

Last verified

Mar, 2026

Keywords

  • PTSD
  • veterans
  • military
  • sleep
  • adrenergic receptor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Wake Forest University Health Sciences on 2026-03-31.