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

This study has been completed.
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Tanja Jovanovic, Emory University
ClinicalTrials.gov Identifier:
NCT01477762
First received: November 17, 2011
Last updated: November 9, 2015
Last verified: November 2015
  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, we 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. We 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
PTSD
Drug: Dexamethasone

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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 Emory University:

Primary Outcome Measures:
  • Psychophysiological responses [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    This study will measure fear-potentiated startle in participants after administration of dexamethasone or placebo.


Secondary Outcome Measures:
  • Cortisol levels [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    Cortisol levels will be assayed from serum samples in response to dexamethasone or placebo.


Enrollment: 150
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
Placebo Comparator: Placebo Drug: Dexamethasone
One time pill administration, at 11pm prior to the study visit
Active Comparator: Dexamethasone Drug: Dexamethasone
0.5 mg, one time administration at 11pm prior to study visit

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. Our recent discovery that cortisol suppression reduces fear responses in PTSD coupled with the development of new fear conditioning paradigms, provides a unique opportunity to interrogate amygdala-HPA interactions to determine aspects of the neurobiological underpinnings of PTSD-related pathology.

AIM 1: Does HPA suppression decrease fear-potentiated startle in subjects with PTSD? Evidence from our preliminary studies suggests that subjects with PTSD have exaggerated expression of fear responses to danger and safety cues after fear acquisition, and that cortisol suppression reduces this pathological fear.

  • 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.

HYPOTHESIS: We predict, based on our preliminary data, that the heightened physiological fear responses in PTSD patients relative to controls will be normalized with cortisol suppression, while cognitive awareness will not be altered. These data will provide new and important tools to further understand the role of dynamic regulation of the HPA axis and its modulation of the human fear response.

AIM 2: Does HPA suppression enhance extinction of fear-potentiated startle in subjects with PTSD? Evidence from our preliminary studies suggests that subjects with PTSD have exaggerated fear responses to the danger cue during fear extinction, and that cortisol suppression facilitates extinction.

  • 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.

HYPOTHESIS: We predict, based on our preliminary data, that the heightened physiological fear responses in PTSD patients relative to controls during extinction will be reduced thereby facilitating extinction with cortisol suppression, while cognitive awareness will not be altered. These data will both extend our understanding of HPA regulation of extinction of fear, as well as provide a direct, testable new therapeutic approach to enhancing extinction (through exposure therapy) in a clinical PTSD population.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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 
Study First Received: November 17, 2011
Last Updated: November 9, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
startle response
fear conditioning
PTSD

Additional relevant MeSH terms:
Stress Disorders, Post-Traumatic
Stress Disorders, Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Dexamethasone acetate
Dexamethasone
Hydrocortisone
Dexamethasone 21-phosphate
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

ClinicalTrials.gov processed this record on August 28, 2016