Cortisol Suppression and Startle Responses in Posttraumatic Stress Disorder (PTSD) (CSS)

March 7, 2017 updated by: Tanja Jovanovic, Emory University

Effects of Cortisol Suppression on Fear-Potentiated Startle in Traumatized Individuals With and Without PTSD

Posttraumatic stress disorder (PTSD) occurs in some people after exposure to events that cause extreme fear or helplessness. The incidence of war zones worldwide and the prevalence of violence in large cities in the U.S., increases the likelihood that people will experience a traumatizing event in their lifetime. About 1 in 10 people who survive such events will develop PTSD, while most people will get better over time. This suggests that some people may have biological vulnerabilities that make it harder for them to recover. One of these biological risk factors may be related to how stress hormones work in people who get sick. Another is how people react to things that make them afraid or nervous, investigators have found that PTSD patients have higher than normal fear reactions. The part of the brain that reacts to fearful stimulation is linked to stress hormones; the purpose of this study is to examine how these systems interact. The study will suppress stress hormones (cortisol) production in one group of participants, while another will get a placebo. When their cortisol is suppressed, the participants will undergo a startle study to see if their fear responses are decreased. Investigators expect that people PTSD will show a normal fear response when their cortisol levels are reduced, similar to people without PTSD. This research can help discover new medicines for people with PTSD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The proposed study will provide innovative tools to tease apart the relationship between amygdala-dependent neurophysiology and HPA-axis sensitivity in a human clinical population. Investigators have discovered that cortisol suppression reduces fear responses in PTSD coupled with the development of new fear conditioning paradigms, providing a unique opportunity to interrogate amygdala-HPA interactions to determine aspects of the neurobiological underpinnings of PTSD-related pathology.

Aim 1a will examine baseline and fear-potentiated startle (FPS) response, as well as cognitive awareness in PTSD patients and traumatized Non-PTSD controls during a fear conditioning experiment 10 hours after dexamethasone administration in a double-blind, placebo controlled crossover design.

Aim 1b will examine the above outcome measures in PTSD patients and controls during a fear conditioning experiment 1 hour after dexamethasone administration in order to control for direct effects of dexamethasone.

Aim 2a will examine fear-potentiated startle (FPS) response in PTSD patients and traumatized Non-PTSD controls during fear extinction, when the fear is acquired 10 hours after dexamethasone administration in a double-blind, placebo controlled crossover design.

Aim 2b will examine the same outcome measures in PTSD patients and controls, when the fear is acquired 1 hour after dexamethasone administration in order to control for direct effects of dexamethasone.

Study Type

Interventional

Enrollment (Actual)

165

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Grady Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Able to give informed consent
  • Willing to participate in initial assessment and 2 full days of interviews and imaging visit
  • Able to understand English and no obvious deficit in comprehension or following directions
  • 18-65 years old

Exclusion Criteria:

  • Mental Retardation (per clinical judgment of study physician)
  • Psychotic Disorder (per clinical judgment of study physician)
  • Acute suicidal ideation
  • Pregnancy
  • Positive urine drug screen
  • Active medical disorders contributing to psychiatric sx e.g. hypo or hyperthyroidism, SLE, advanced cirrhosis, etc. (per clinical judgment of study physician)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: PTSD Negative
Participants who do not have PTSD will receive placebo and dexamethasone in random order for the duration of two consecutive study visits separated by at least one month.
Drug: Dexamethasone
One tablet of 0.5 mg dexamethasone will be taken ten hours prior to completing study assessments.
Drug: Placebo
One placebo tablet will be taken ten hours prior to completing study assessments.
EXPERIMENTAL: PTSD Positive
Participants with PTSD will receive placebo and dexamethasone in random order for the duration of two consecutive study visits separated by at least one month.
Drug: Dexamethasone
One tablet of 0.5 mg dexamethasone will be taken ten hours prior to completing study assessments.
Drug: Placebo
One placebo tablet will be taken ten hours prior to completing study assessments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Baseline Startle Magnitude During Fear Conditioning
Time Frame: 10 hours after drug administration
The study measured the acoustic startle response magnitude to a sudden noise using electromyography of the eyeblink muscle. This response magnitude was used as the individual's baseline to compare to the startle magnitude to the danger signal to see if fear conditioning had occurred.
10 hours after drug administration
Mean Startle Magnitude to Danger Signal During Fear Conditioning
Time Frame: 10 hours after drug administration
The acoustic startle response magnitude was measured using electromyography recordings of the eyeblink muscle when a sudden tone was delivered through headphones in the presence of a stimulus that was paired with an aversive outcome (i.e. the danger signal). If an individual showed successful fear learning, then startle to the danger signal would be greater than baseline startle.
10 hours after drug administration
Mean Fear-potentiated Startle to Danger Signal During Early Extinction
Time Frame: 10 hours after drug administration
Fear-potentiated startle was measured as a difference score between the startle to danger signal and the baseline. This difference score reflects the degree of fear response at the beginning of extinction.
10 hours after drug administration
Mean Fear-potentiated Startle to Danger Signal During Late Extinction
Time Frame: 10 hours after drug administration
This measures the level of fear-potentiated startle (the difference between startle magnitude to the danger signal and baseline startle magnitude) at the end of extinction. Because the danger signal is no longer paired with the aversive stimulus like it was during the conditioning phase, the fear response should decrease from early to late extinction in individuals who show intact extinction learning.
10 hours after drug administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Tanja Jovanovic, PhD, Emory University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2011

Primary Completion (ACTUAL)

July 1, 2015

Study Completion (ACTUAL)

July 1, 2015

Study Registration Dates

First Submitted

November 17, 2011

First Submitted That Met QC Criteria

November 21, 2011

First Posted (ESTIMATE)

November 23, 2011

Study Record Updates

Last Update Posted (ACTUAL)

April 18, 2017

Last Update Submitted That Met QC Criteria

March 7, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00051911
  • 1R21MH092576-01A1 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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