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PTSDPhase 2NCT04924166

PTSD Prevention Using Oral Hydrocortisone

A Phase 2 study testing Hydrocortisone in people with PTSD and Acute Stress Disorder, run by Rachel Yehuda at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

There is currently no evidence-based intervention for individuals exposed to trauma that is designed to aid recovery and prevent the development of post-traumatic stress disorder (PTSD). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hydrocortisone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
201 participants
Where
3 sitesin 2 countries
Study dates
12 Jan 2022to 6 Jul 2025
Phase
Phase 2
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years
  • Weight: 99 lb - 242 lbs
  • Experienced a traumatic event less than 6 hours ago
  • Secondary Inclusion Criteria:
  • ED staff note marked anxiety emotional distress and or dissociation in relation to index trauma as assessed by meeting a minimum of 2 out of 4 of the peritraumatic characteristics that have been associated with the development of PTSD below:
  • Anxiety Visual Analog Scale minimum score of 4 on a scale of 0 to 10
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  • Peritraumatic dissociation (PDEQ) with a cut-point of 15 (lowest possible score is 10)
  • Peritraumatic distress (Peritraumatic Distress Inventory) (PDI) with a cut-point of 15 (lowest possible score is 0)
  • Heart rate at 80 bpm or more

Who cannot join

  • Severe physical injury as assessed with the Abbreviated Injury Scale (AIS > 2); Examples include severe burn injury, life-threatening medical or surgical condition, condition requiring surgical intervention under general anesthesia, as indicated by clinical judgment.
  • Inability to provide informed consent or cooperate with the screening or collection of initial measures.
  • Intoxication to a degree that would interfere with the ability to provide informed consent or high level or intoxication reported at the time of trauma.
  • Moderate to severe head injury associated with current trauma exposure as defined by a loss of consciousness >30 minutes following injury.
  • Medical conditions e.g., Cushing's syndrome, current acute infectious or viral disease, tuberculosis, unstable diabetes or hypertension, myasthenia gravis, heart failure.
  • Currently taking oral steroids
Show all 14Show fewer
  • Use of benzodiazepine within 24 hours of trauma exposure will not be eligible to participate in the study
  • Individuals prescribed a narcotic medication to alleviate acute pain in the ED will not be eligible to participate in the treatment study.
  • Weight below 45kg or above 110 kg (99 lbs - 242 lbs)
  • Pregnancy (a urine pregnancy test will be performed in the ED)
  • Individuals experiencing on-going trauma (i.e., domestic violence).
  • Reported diagnoses of schizophrenia, bipolar I disorder, or other psychotic illness.
  • Current or past history of dementia, amnesia or other cognitive disorder predating trauma exposure
  • Residence outside local area, which would hinder attendance at follow up visits due to long travel time.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Mount Sinai Morningside Emergency Department

    New York, New York, 10025

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

Israel1 site

  • The Chaim Sheba Medical Center

    Ramat Gan

Other trials in Israel

About this study

Official title: PTSD Prevention Using Oral Hydrocortisone in the Immediate Aftermath of Trauma

There is currently no evidence-based intervention for individuals exposed to trauma that is designed to aid recovery and prevent the development of post-traumatic stress disorder (PTSD). This randomized control trial proposes to test a one-time prophylactic treatment for the prevention of symptoms of PTSD and related mental health disturbances and the promotion of resilience using a single dose of hydrocortisone (HCORT) or placebo, administered within six hours of trauma exposure. People at risk for PTSD have demonstrated low cortisol levels before and in the aftermath of traumatic exposures and lower cortisol levels have also been observed in combat veterans with PTSD. Administering HCORT at the time of trauma would help boost the body's natural stress recovery systems to facilitate resilience.

Participants who present to the emergency department following trauma exposure and report high distress, panic, anxiety or dissociation will be invited to participate in this clinical trial. 220 trauma survivors will be randomized and recruited at two locations: Mount Sinai Hospital in New York City, US, and a civilian/military hospital in Tel Hashomer, Israel. Trauma survivors will be assessed at 2, 6, 12 and 28 weeks post-treatment. HCORT closely resembles cortisol produced in the adrenal glands and released during stress.

It is hypothesized that HCORT treatment will result in an accelerated decline in the presence and severity of PTSD and related mental health symptoms compared to the placebo group. Blood samples will be collected for analysis of potential biomarkers to obtain more information about the mechanisms of action of this intervention. The information obtained will be relevant in determining whether early intervention with a single dose of HCORT, compared to placebo, administered within several hours following trauma exposure, will reduce the risk of developing PTSD in trauma survivors.

Read the detailed description

Preliminary findings using HCORT in PTSD prevention have been encouraging. However, it is imperative to provide a more definitive study of HCORT effects across a wide range of demographic and traumatic exposures. In addition, prior studies used a single IV dose of HCORT administered in the Emergency Department (ED) and it is critical to determine whether effects would be comparable using oral HCORT. The advantage of an oral prophylactic is that a pill is a portable prophylactic that could be carried by first responders, military personnel and other people whose occupations expose them to risk of trauma exposure.

The results of this RCT will add to the existing literature in several important ways. The study will be larger in scope, and will target a more extensive biological profile to elucidate mechanisms of action. To maximize enrollment within a shorter period of time, the study will be conducted at two sites. The first site is the ED at the Mount Sinai Hospital, located in East Harlem in New York City (NYC), and the second is the ED at Sheba Medical Center in Israel. These sites allow for the evaluation of a broad range of trauma survivors. In NYC, the large urban ED provides services to a diverse population with respect to race, ethnicity and trauma exposure. At Sheba Medical Center, those who present to the ED are active duty, reserve military personnel and civilians. By including both sites, the investigators will be able to evaluate the effectiveness of the intervention in a global and more ethnically diverse sample that includes people exposed to a wide variety of traumas. Prior research and results from the researchers' intervention studies indicate the importance of recruiting participants who are distressed, including those expressing feelings of dissociation, when they present to the ED (i.e., such people are at greater risk for the development of PTSD) following trauma exposure that is life-threatening or causes injury. For this reason, the current study will select participants who meet a specified threshold for acute distress following trauma exposure.

There is accumulating evidence to support the potential mechanism of action of the administration of HCORT on achieving homeostasis and resilience following exposure to a critical traumatic incident. In this interventional study, the researchers will collect blood samples for the purpose of conducting further analyses of biomarkers to obtain more information about the mechanisms of action of this intervention and to enhance knowledge about mechanisms associated with resilience. These aims will be achieved by assessing candidate neuroendocrine biomarkers as well as related molecular networks (e.g., genome wide methylation and expression) relevant to PTSD risk, and resilience.

If the current trial using oral administration of HCORT is successful, it will generate a viable, safe, portable, lightweight, prophylactic treatment that can be self-administered and made available to military personnel, first responders and other civilians exposed to extreme trauma.

Being tested
Placebo, Hydrocortisone
Keywords
prophylaxis, randomized controlled trial
Medical subject headings
Stress Disorders, Post-Traumatic, Stress Disorders, Traumatic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Inactive dose of capsules that appear identical to active dose

  • HydrocortisoneDrug

    Also called HCORT

    Hydrocortisone 180 mg in capsule form

Study groups in NCT04924166
Study groupRoleWhat they receive
PlaceboPlacebo comparatormatching capsule PO
Receives: Drug: Placebo
HCORTActive comparator180 mg capsule PO
Receives: Drug: Hydrocortisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinician Administered PTSD Scale (CAPS)

    PTSD diagnosis and symptom severity determined by clinical ratings using the Clinician Administered PTSD Scale (CAPS). Total score range from 0 to 80, higher score indicates higher severity.

    Measured: Up to 7 months

Secondary outcomes (6)

  1. The Structured Clinical Interview for DSM-5 (SCID)

    The Structured Clinical Interview for DSM-5 (SCID) assesses the presence of other psychiatric diagnoses and comorbid conditions that can develop in response to trauma exposure, including depression, acute stress disorder and substance use disorder. In addition, participants will complete self-ratings at each time point to assess sleep quality, quality of life, and mood.

    This is not a scale. Each is answered as absence or presence of the diagnosis in the past 30 days.

    Measured: Up to 7 months

  2. Pittsburgh Sleep Quality Index (PSQI)

    Sleep quality is disrupted in PTSD and other mental health problems (e.g., depression). Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI). Rating scores for PSQI range from 0 to 21.

    Measured: Up to 7 months

  3. The Sheehan Disability Scale (SDS)

    Functional disability - The Sheehan Disability Scale (SDS) addresses the impact of symptoms of PTSD on work, social, and family functioning within the last 7 days.

    Measured: Up to 7 months

  4. Change in The Clinical Global Impression - Severity (CGI-S)

    CGI-S rating scores range from 'Normal, not at all ill = 0' to 'Among the most ill patients = 7'.

    Measured: Baseline and 7 months

  5. Change in the Clinical Global Impression - Improvement (CGI-I)

    CGI-I rating scores range from 'Not assessed = 0' to 'Very much worse = 7'

    Measured: Baseline and 7 months

  6. Montgomery-Asberg Depression Rating Scale (MADRS)

    Depressive symptoms Clinician ratings of depression will be obtained with the Montgomery-Asberg Depression Rating Scale (MADRS) consisting of 10 items that assess core symptoms of depression. Scores range from 0 to 60, with higher scores indicative of higher depressive symptoms.

    Measured: Up to 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2021
  2. Study start12 Jan 2022
  3. Primary completion6 Jul 2025
  4. Study completion6 Jul 2025

Resources

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a double-blind, randomized, placebo-controlled trial in which trauma victims are randomized to receive a single oral dose of HCORT or placebo within the first six hours following trauma exposure. This design permits testing of the primary study hypothesis that HCORT administration within hours post-trauma facilitates physiological recovery, thereby promoting resilience.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
201 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04924166
Sponsor's protocol ID
GCO 18-0090
Other IDs
W81XWH1910138
Status last verified
Dec 2025
First submitted
7 Jun 2021
Last updated
19 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Publications

  • Zohar J, Yahalom H, Kozlovsky N, Cwikel-Hamzany S, Matar MA, Kaplan Z, Yehuda R, Cohen H. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies. Eur Neuropsychopharmacol. 2011 Nov;21(11):796-809. doi: 10.1016/j.euroneuro.2011.06.001. Epub 2011 Jul 8.

    PubMed 21741804

  • Ozer EJ, Best SR, Lipsey TL, Weiss DS. Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. Psychol Bull. 2003 Jan;129(1):52-73. doi: 10.1037/0033-2909.129.1.52.

    PubMed 12555794

  • Yehuda R, Bryant R, Marmar C, Zohar J. Pathological responses to terrorism. Neuropsychopharmacology. 2005 Oct;30(10):1793-805. doi: 10.1038/sj.npp.1300816.

    PubMed 16012535

  • Cohen H, Kaplan Z, Zohar J. [CAN POST-TRAUMATIC STRESS DISORDER BE PREVENTED WITH GLUCOCORTICOIDS?]. Harefuah. 2016 Dec;155(12):757-761. Hebrew.

    PubMed 28530340

  • Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C. Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms. Cochrane Database Syst Rev. 2024 May 20;5(5):CD013613. doi: 10.1002/14651858.CD013613.pub2.

    PubMed 38767196

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hydrocortisone in people with PTSD and Acute Stress Disorder, run by Rachel Yehuda at 3 sites in 2 countries.

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 9 inclusion and 14 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 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Israel. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Clinician Administered PTSD Scale (CAPS) (time frame: Up to 7 months). 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 NCT04924166, which also lists 5 linked publications.

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 19 Mar 2026.

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PTSD Prevention Using Oral Hydrocortisone | AzTrials