The Use of Propranolol to Block Memory Reconsolidation in PTSD

Study Overview
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Brief Summary
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The purpose of this investigation is to see if propranolol will reduce the psychophysiological hyperactivation associated with memories of combat stress in Veterans with Posttraumatic Stress Disorder.

Detailed Description
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The goal of this translational research project is to generate a pilot sample of data from an investigation of a novel therapeutic approach to post traumatic stress disorder (PTSD). Current treatments for PTSD include exposure and other aspects of cognitive therapy as well as drug therapies based on serotonin-reuptake inhibiting antidepressant agents. However, these treatments are often unsuccessful, and symptoms in affected individuals may persist for decades. The central hypothesis guiding this research project posits that acquired fear responses, such as those in PTSD, when reactivated by recall become sensitive to noradrenergic modulation and thus may be permanently attenuated by blocking noradrenergic transmission. Further, we predict that this attenuation will facilitate subsequent therapy. In the current study, we will be investigating this model in three groups of Veterans of either Operation Iraqi Freedom or Operation Enduring Freedom (OIF/OEF) with PTSD: 1) Individuals who receive propranolol following recall of a traumatic memory (Propranolol-trauma); 2) Individuals who receive a placebo following recall of a traumatic memory (Placebo-trauma), and; 3) Individuals who receive propranolol following recall of an affective neutral memory (Propranolol-neutral). In addition, traumatic memory recall will be psychophysiologically assessed by measuring Veterans' facial corrugator electromyography (EMG), skin conductance, blood pressure and cardiovascular inter-beat interval responses pre- and one month post-medication administration.

Official Title
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The Use of Propranolol to Block Memory Reconsolidation in Post Traumatic Stress Disorders (PTSD)

Conditions
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Posttraumatic Stress Disorders

Intervention / Treatment
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* Drug: Propranolol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants will meet the clinical criteria of PTSD (DSM IVTR) secondary to combat exposure. Exclusion Criteria: Current illicit substance use or alcohol consumption, as determined by urine toxicology and alcohol breath test. Any diagnosis of current comorbid psychotic disorders, bipolar disorder, or illicit substance or alcohol abuse or dependence. Any current prescription medication usage or supplement (dietary or herbal) usage that is contraindicated with propranolol. Active enrollment into any psychiatric or psychological treatment. Any condition that contraindicates the use of propranolol, such as: history of bronchial asthma. heart block. sinus bradycardia. congestive heart failure. insulin-dependent diabetes. initial systolic blood pressure < 100 mmHg. Hyperthyroidism. Thyroid disease. Renal or liver impairment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Propranolol following traumatic memory | Drug: Propranolol<br>* 40mg propranolol, followed 2 hrs after with 60mg propranolol, immediately following memory recollection<br>|
| Active Comparator: 2<br>Propranolol following neutral memory | Drug: Propranolol<br>* 40mg propranolol, followed 2 hrs after with 60mg propranolol, immediately following memory recollection<br>|
| Placebo Comparator: 3<br>Placebo following traumatic memory | Drug: Placebo<br>* 40mg placebo, followed 2 hrs after with 60mg placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Facial corrugator EMG |  | Change in Facial corrugator EMG from baseline at 1 month post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CAPS score |  | Change in CAPS score from baseline at 1 month post-intervention | 
| PCL-M score |  | Change in PCL-M score from baseline at 1 month post-intervention |