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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01477762
First Posted: November 23, 2011
Last Update Posted: April 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Tanja Jovanovic, Emory University
  Purpose
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.

Condition Intervention
Post Traumatic Stress Disorder Drug: Dexamethasone Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Cortisol Suppression on Fear-Potentiated Startle in Traumatized Individuals With and Without PTSD

Resource links provided by NLM:


Further study details as provided by Tanja Jovanovic, Emory University:

Primary Outcome Measures:
  • 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.

  • 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.

  • 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.

  • 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.


Enrollment: 165
Study Start Date: November 2011
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01477762


Locations
United States, Georgia
Grady Health System
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Tanja Jovanovic, PhD Emory University
  More Information

Additional Information:
Publications:
Responsible Party: Tanja Jovanovic, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT01477762     History of Changes
Other Study ID Numbers: IRB00051911
1R21MH092576-01A1 ( U.S. NIH Grant/Contract )
First Submitted: November 17, 2011
First Posted: November 23, 2011
Results First Submitted: August 25, 2016
Results First Posted: April 18, 2017
Last Update Posted: April 18, 2017
Last Verified: March 2017

Keywords provided by Tanja Jovanovic, Emory University:
startle response
fear conditioning
PTSD

Additional relevant MeSH terms:
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Dexamethasone acetate
Dexamethasone
Hydrocortisone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action