Using low-dose clonidine to treat PTSD in veterans

Repurposing Low-Dose Clonidine for PTSD in Veterans

This study is testing if a low dose of clonidine can help veterans with PTSD feel better and improve their sleep and daily activities.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Wake Forest University Health Sciences (Academic / other)
• Locations: 1 site (Wauwatosa, Wisconsin)
• Trial ID: NCT04877093 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of low-dose clonidine on military veterans diagnosed with Posttraumatic Stress Disorder (PTSD). The study aims to determine if clonidine can improve various PTSD symptoms, including those affecting daytime functioning and sleep. Veterans will be randomly assigned to receive either clonidine or a placebo, and their symptoms will be assessed using standardized questionnaires. The trial addresses the need for more effective treatments for PTSD, particularly for veterans who often do not respond well to current first-line therapies.

Who should consider this trial

Good fit: Ideal candidates for this study are US military veterans aged 18 and older who have a confirmed diagnosis of PTSD.

Not a fit: Patients who are pregnant, breastfeeding, or at moderate to high risk of suicide may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new, effective option for veterans suffering from PTSD, potentially improving their quality of life.

How similar studies have performed: While the use of clonidine for PTSD is not widely tested, there is some preliminary evidence suggesting that targeting noradrenergic pathways may be beneficial, making this approach promising yet relatively novel.

Eligibility criteria

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

Where this trial is running

Wauwatosa, Wisconsin

• Aurora Psychiatric Hospital — Wauwatosa, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Gregory Burek, MD, MS — Wake Forest University Health Sciences
• Study coordinator: Kevin Petranu

Conditions PTSD; Posttraumatic Stress Disorder; Sleep; veterans; military; sleep; adrenergic receptor