The Use of Propranolol to Block Memory Reconsolidation in PTSD

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

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.

Study Overview

• Status: Terminated
• Conditions: Posttraumatic Stress Disorders
• Intervention / Treatment: Drug: Propranolol; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • John D Dingell VA Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: John D. Dingell VA Medical Center; New York University
• Investigators: Principal Investigator: Deane Aikins, PhD, Wayne State University

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 1, 2008
• First Submitted That Met QC Criteria: February 8, 2008
• First Posted (Estimate): February 11, 2008

Study Record Updates

• Last Update Posted (Estimate): November 1, 2016
• Last Update Submitted That Met QC Criteria: October 31, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: HIC 0703002443

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No