Post Traumatic Stress DisorderCSSNCT01477762
Cortisol Suppression and Startle Responses in Posttraumatic Stress Disorder (PTSD)
A study testing Dexamethasone in people with Post Traumatic Stress Disorder, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post Traumatic Stress Disorder
- What is being tested?
- Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 165 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Jul 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Post Traumatic Stress Disorder
- Being tested
- Dexamethasone, Placebo
- Keywords
- startle response, fear conditioning, PTSD
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
One tablet of 0.5 mg dexamethasone will be taken ten hours prior to completing study assessments.
PlaceboDrug
One placebo tablet will be taken ten hours prior to completing study assessments.
| Study group | Role | What they receive |
|---|---|---|
| PTSD Negative | Active comparator | 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. Receives: Drug: Dexamethasone; Drug: Placebo |
| PTSD Positive | Experimental | 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. Receives: Drug: Dexamethasone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Baseline Startle Magnitude During Fear Conditioning
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.
Measured: 10 hours after drug administration
Mean Startle Magnitude to Danger Signal During Fear Conditioning
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.
Measured: 10 hours after drug administration
Mean Fear-potentiated Startle to Danger Signal During Early Extinction
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.
Measured: 10 hours after drug administration
Mean Fear-potentiated Startle to Danger Signal During Late Extinction
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.
Measured: 10 hours after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Tanja Jovanovic, Emory University
- Investigators
- Tanja Jovanovic, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01477762
- Sponsor's protocol ID
- IRB00051911
- Other IDs
- 1R21MH092576-01A1
- Acronym
- CSS
- Status last verified
- Mar 2017
- First submitted
- 17 Nov 2011
- Last updated
- 18 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21601366
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Cortisol Suppression on Fear-Potentiated Startle in Traumatized Individuals With and Without PTSD
- ClinicalTrials.gov ID
- NCT01477762
- Acronym / sponsor ID
- CSS / IRB00051911
- Conditions
- Post Traumatic Stress Disorder
- Keywords
- startle response, fear conditioning, PTSD
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Nov 2011
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 23 Nov 2011 (estimated)
- Results
- Posted 18 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PTSD Negative | Active comparator | Drug: Dexamethasone, Drug: PlaceboParticipants 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 | Experimental | Drug: Dexamethasone, Drug: PlaceboParticipants with PTSD will receive placebo and dexamethasone in random order for the duration of two consecutive study visits separated by at least one month. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- Mental Retardation (per clinical judgment of study physician)
- Psychotic Disorder (per clinical judgment of study physician)
- Acute suicidal ideation
- Pregnancy
- Positive urine drug screen
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneOne tablet of 0.5 mg dexamethasone will be taken ten hours prior to completing study assessments. | Drug | PTSD Negative, PTSD Positive |
| PlaceboOne placebo tablet will be taken ten hours prior to completing study assessments. | Drug | PTSD Negative, PTSD Positive |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21601366Jovanovic 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tanja Jovanovic, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dexamethasone in people with Post Traumatic Stress Disorder, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Baseline Startle Magnitude During Fear Conditioning (time frame: 10 hours after drug administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01477762, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2017.