NCT04877093 · Wake Forest University Health Sciences
Repurposing Low-Dose Clonidine for PTSD in Veterans
What this study is about
Hypothesis: Veterans with PTSD prescribed clonidine will demonstrate improvements in PTSD symptoms, including daytime, nighttime, and sleep-related behaviors.
View original scientific description
Hypothesis: Veterans with PTSD prescribed clonidine will demonstrate improvements in PTSD symptoms, including daytime, nighttime, and sleep-related behaviors.
Interventions
DRUG
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.
OTHER
Placebo
Blinded placebo capsules will be provided to participants.
Primary outcome measures
Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) at 6 weeks into phase
Time frame: Week 6 of Current Phase
Scored 0-21, where higher scores indicate worse sleep quality.
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
Measures PTSD symptoms on sleep, with each question scored 1-4, where higher scores indicate more severe symptoms.
Change from Baseline in PTSD Checklist-Military Version (PCL-5) at 6 weeks into phase
Time frame: Week 6 of Current 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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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:
- Other opiates/analgesics
- Barbiturates
- Other sedatives/, hypnotics, or tranquilizers
- Amphetamines
- Hallucinogens
- 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
- 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
Where
- Wauwatosa, Wisconsin
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 31, 2026 · Source of record for eligibility and locations