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

Not Applicable

Completed

• Conditions: Post Traumatic Stress Disorder
• Interventions: Drug: Dexamethasone; Drug: Placebo

• Registration Number: NCT01477762
• Lead Sponsor: Emory University

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2011-11-17
• Study First Submitted QC: 2011-11-21
• Study First Posted: 2011-11-23
• Primary Completion: 2015-07
• Study Completion: 2015-07
• Results First Submitted: 2016-08-25
• Status Verified: 2017-03
• Results First Submitted QC: 2017-03-07
• Last Update Submitted: 2017-03-07
• Results First Posted: 2017-04-18
• Last Update Posted: 2017-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 165

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
PTSD Negative	Placebo	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.
PTSD Positive	Placebo	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.
PTSD Negative	Dexamethasone	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.
PTSD Positive	Dexamethasone	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.

Primary Outcome Measures

Name	Time	Method
Mean Baseline Startle Magnitude During Fear Conditioning	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.
Mean Startle Magnitude to Danger Signal During Fear Conditioning	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.
Mean Fear-potentiated Startle to Danger Signal During Early Extinction	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.
Mean Fear-potentiated Startle to Danger Signal During Late Extinction	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.

Trial Locations

Locations (1)

Grady Health System; 🇺🇸 Atlanta, Georgia, United States