Carvedilol Versus Placebo for Treatment in Post Traumatic Stress Disorder (PTSD)

Study Overview
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Brief Summary
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The investigators hypothesize that carvedilol, at less then therapeutic doses for cardiac effect, will reduce symptoms of Post Traumatic Stress Disorder.

Detailed Description
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This initial proof of concept trial design is intended to explore multiple variables. Fist, it is intended to determine if carvedilol has any statistically significant effect over placebo on the various overall symptoms, symptom clusters, or individual symptoms of post traumatic stress disorder. Next, the flexible dosing trial design is aimed to detect the therapeutic dose, or dosing range for carvedilol when used in the treatment of PTSD

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Study to Assess the Safety and Efficacy of Carvedilol Versus Placebo in the Treatment of Post Traumatic Stress Disorder

Conditions
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Post-Traumatic Stress Disorder

Intervention / Treatment
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* Drug: Carvedilol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Post Traumatic Stress Disorder according to DSM-IV Must be able to speak, read and understand the English language and be able to provide written informed consent Exclusion Criteria: current, unstable and significant medical condition/illness bronchial asthma or related bronchospastic condition AV block Sick Sinus Syndrome Bradycardia Peripheral hear disease Unstable thyroid disorder History of seizure disorder Females who are pregnant, lactating or planning to become pregnant Bipolar Schizophrenia Dementia Intolerance or hypersensitivity to alpha or beta blockers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: carvedilol<br>Patients randomized to carvedilol will be administered doses ranging from 6.25 to 15.625 mg/day using a flexible-dosing model. After a 1 week titration, investigators my increase daily dose by 6.25 mg/day at weeks 1 and 2 for a maximum dose of 15.625 mg/day. Weeks 3-4 will patients will remain on a stable, tolerable dose. At week 5 patients will have a 1 week taper. | Drug: Carvedilol<br>* Oral, twice daily dosing using 3.125 mg tablets. 1 week titration (6.25 mg/day)prior to a 3 week flexible dosing option ranging from 6.25 mg/day to 15.625 mg/day followed by a 1 week taper (6.25 mg/day).<br>* Other names: Coreg(R);|
| Placebo Comparator: Sugar Pill<br>Patients randomized to placebo will follow same dosing guidelines as if they were in the active comparator arm, carvedilol. | Drug: Placebo<br>* Non active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Davidson Trauma Scale (DTS) | The DTS is a 17-item self report measure to assess the 17 DMS-IV symptoms of PTSD. Respondants are asked to identify the trauma that is most disturbing to them and to rate, in the past week, how much trouble they hav had with each symptom. The DTS can be used to make a preliminatry determination about whether the symptoms meet DSM criteria for PTSD, or scores can be calculated for each of the 3 PTSD symptom clusters. The DTS will be assessed at each study visit (visit 1, 2, 3, 4, 5, 6 and 7). The primary efficacy outcome will be change from baseline (visit 2) to week 5 (visit 7). | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician Administered PTSD Scale (CAPS) | The CAPS was developed at the National Center for PTSD and has become the gold standard for assessing Post Traumatic Stress Disorder. It is a user-friendly structured interview for screening, differential diagnosis, comfirming PTSD diagnosis or identifying Acute Stress Disorder. The CAPS will be assessed at the screening visit and again at week 5 (vist 7). Change scores (from screening to week 5) will be secondary efficacy measures. | 6 Weeks | 
| Insomnia Severity Index (ISI) | The ISI is a 7-item patient rated questionnaire that evaluates severity of sleep onset and maintenance difficulties, satisfaction with current sleep pattern interference with daily functioning, appearance of impairment attributed to the sleep problem, and the degree of concern caused by insomnia. Secondary outcome measures using the ISI will be determined using change scores from baseline to week 5 (visit 7) | 5 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTSD, Anxiety, Trauma, Assault, Victim, Witness, Post Traumatic Stress Disorder, Combat veteran, Flashbacks, Nightmares, Sleep Disturbance, Hyperarousal, Numbness, Avoidance