Clinical trial NCT01477762: Cortisol Suppression and Startle Responses in Posttraumatic Stress Disorder (PTSD)
Official title: Effects of Cortisol Suppression on Fear-Potentiated Startle in Traumatized Individuals With and Without PTSD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post Traumatic Stress Disorder
Keywords: startle response
fear conditioning
PTSD
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2011-11-23
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Mean Baseline Startle Magnitude During Fear Conditioning
timeFrame: 10 hours after drug administration
measure: Mean Startle Magnitude to Danger Signal During Fear Conditioning
timeFrame: 10 hours after drug administration
measure: Mean Fear-potentiated Startle to Danger Signal During Early Extinction
timeFrame: 10 hours after drug administration
measure: Mean Fear-potentiated Startle to Danger Signal During Late Extinction
timeFrame: 10 hours after drug administration
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
Study officials:
affiliation: Emory University
name: Tanja Jovanovic, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jovanovic T, Phifer JE, Sicking K, Weiss T, Norrholm SD, Bradley B, Ressler KJ. Cortisol suppression by dexamethasone reduces exaggerated fear responses in posttraumatic stress disorder. Psychoneuroendocrinology. 2011 Nov;36(10):1540-52. doi: 10.1016/j.psyneuen.2011.04.008. Epub 2011 May 20.