PTSD Prevention Using Oral Hydrocortisone

NCT04924166 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: GCO 18-0090W81XWH1910138
• Study Type: interventional
• Target: 201
• Locations: 2 countries
• Sites: 3

Brief 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). 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.

Conditions

PTSD; Acute Stress Disorder; Trauma-related Stressor

Keywords

prophylaxis; randomized controlled trial

Outcome Measures

Primary Outcomes (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.

  Up to 7 months

Secondary Outcomes (6)

• The Structured Clinical Interview for DSM-5 (SCID)

  Up to 7 months

• Pittsburgh Sleep Quality Index (PSQI)

  Up to 7 months

• The Sheehan Disability Scale (SDS)

  Up to 7 months

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

  Baseline and 7 months

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

  Baseline and 7 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

matching capsule PO

Drug: Placebo

HCORT

ACTIVE COMPARATOR

180 mg capsule PO

Drug: Hydrocortisone

Interventions

Placebo DRUG

Inactive dose of capsules that appear identical to active dose

Placebo

Hydrocortisone DRUG

Hydrocortisone 180 mg in capsule form

Also known as: HCORT

HCORT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Weight: 99 lb - 242 lbs
• Experienced a traumatic event less than 6 hours ago
• 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
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• The Chaim Sheba Medical Center: collaborator
• Rachel Yehuda: lead
• James J. Peters Veterans Affairs Medical Center: collaborator

Study Sites (3)

Mount Sinai Morningside Emergency Department

New York, New York, 10025, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

The Chaim Sheba Medical Center

Ramat Gan, Israel

Location

Related Publications (5)

• 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.

  PMID: 21741804 BACKGROUND

• 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.

  PMID: 12555794 BACKGROUND

• 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.

  PMID: 16012535 BACKGROUND

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

  PMID: 28530340 BACKGROUND

• 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.

  PMID: 38767196 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Stress Disorders, Traumatic, Acute

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Rachel Yehuda, PhD

  Icahn School of Medicine at Mount Sinai; James J. Peters Veterans Affairs Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: June 11, 2021
• Study Start: January 12, 2022
• Primary Completion: July 6, 2025
• Study Completion: July 6, 2025
• Last Updated: March 19, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. For individual participant data meta-analysis. Other Proposals may be submitted up to 36 months following article publication.

Locations

IL (1); US (2)