Hydrocortisone for Preventing PTSD

Not currently recruiting at 2 trial locations

Overseen By Evelyn Alkin, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rachel Yehuda

Must not be taking: Oral steroids, Benzodiazepines, Narcotics

Disqualifiers: Severe injury, Pregnancy, Schizophrenia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: Single dose

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a single dose of hydrocortisone, administered shortly after a traumatic event, can prevent PTSD, a mental health condition triggered by trauma. The goal is to determine if this treatment can calm the body's stress response and reduce PTSD symptoms. Participants will receive either hydrocortisone or a placebo (a pill without active medication) within six hours of the trauma. The trial seeks individuals who have recently experienced a traumatic event, feel high distress or panic, and can visit one of the study locations for follow-up checks. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking oral steroids or have used benzodiazepines within 24 hours of trauma exposure.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that hydrocortisone (HCORT) is generally safe for people. Some studies suggest that low doses of hydrocortisone might help prevent PTSD in those who have recently experienced trauma. Although few studies exist, early findings indicate it is safe and could help the body manage stress better during difficult times.

The FDA has already approved hydrocortisone for other uses, such as treating serious skin problems, indicating its safety when used properly. While side effects are possible, current evidence suggests that hydrocortisone is usually safe for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Unlike the standard treatments for PTSD, which usually involve therapy and medications like SSRIs, hydrocortisone is being explored for its potential to prevent PTSD rather than just treat it after symptoms appear. Hydrocortisone is a steroid hormone that might help by reducing inflammation and stress responses in the brain right after a traumatic event. Researchers are excited about this approach because it targets the condition at its root, potentially stopping PTSD before it fully develops, and offering a proactive rather than reactive solution.

What evidence suggests that hydrocortisone might be an effective treatment for PTSD?

Research has shown that hydrocortisone, which participants in this trial may receive, can help reduce PTSD symptoms. One study found that people who took hydrocortisone after experiencing trauma had fewer PTSD symptoms than those who took a placebo, a pill with no active medicine. This improvement appeared at 2 weeks and persisted at 1 and 3 months. Hydrocortisone may help by enhancing the body's natural stress response, potentially increasing resilience after a traumatic event. Overall, hydrocortisone appears to be a promising option for preventing PTSD in trauma survivors. ^{1 2 4 6 7}

Who Is on the Research Team?

Rachel Yehuda, PhD

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for adults who've recently experienced trauma, feel highly distressed or disconnected, and have a heart rate of 80 bpm or more. They must weigh between 99-242 lbs and not be severely injured, intoxicated, pregnant, on steroids or benzodiazepines, nor have certain chronic diseases or mental health conditions.

Inclusion Criteria

You experienced significant emotional distress during or after a traumatic event, as measured by a questionnaire with a score of 15 or higher.

My weight is between 99 and 242 lbs.

I experienced a traumatic event within the last 6 hours.

Exclusion Criteria

I have not been prescribed narcotics for acute pain in the emergency department.

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.

I live too far to attend follow-up visits without difficulty.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive a single dose of hydrocortisone or placebo within six hours of trauma exposure

Single dose

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 2, 6, 12, and 28 weeks post-treatment

28 weeks

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Hydrocortisone
• Placebo

Trial Overview The study tests if a single dose of hydrocortisone (HCORT), given within six hours after trauma can prevent PTSD compared to a placebo. It's randomized with assessments at multiple intervals post-treatment to measure the decline in PTSD symptoms and related mental health issues.

How Is the Trial Designed?

Group I: HCORT Active Control 1 Intervention

180 mg capsule PO

Group II: Placebo Placebo Group 1 Intervention

matching capsule PO

Hydrocortisone is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Hydrocortisone for:

• Adrenal insufficiency
• Allergic reactions
• Asthma
• Severe acute pancreatitis

Approved in United States as Hydrocortisone for:

• Adrenal insufficiency
• Allergic reactions
• Asthma
• Severe acute pancreatitis

Approved in Canada as Hydrocortisone for:

• Adrenal insufficiency
• Allergic reactions
• Asthma
• Severe acute pancreatitis

Who Is Running the Clinical Trial?

Rachel Yehuda

Lead Sponsor

Trials

2

Recruited

320+

The Chaim Sheba Medical Center

Collaborator

Trials

20

Recruited

7,400+

James J. Peters Veterans Affairs Medical Center

Collaborator

Trials

59

Recruited

2,900+

Published Research Related to This Trial

In a study of 63 male veterans, oral administration of 20mg hydrocortisone reduced the fear-potentiated startle response, indicating a potential fear-inhibiting effect of cortisol.

The reduction in startle responses occurred regardless of whether the veterans had PTSD, suggesting that hydrocortisone may influence the body's stress response system, which could help in understanding resilience to traumatic stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrocortisone suppression of the fear-potentiated startle response and posttraumatic stress disorder. Miller, MW., McKinney, AE., Kanter, FS., et al.[2021]

In a pilot study involving 24 military veterans, hydrocortisone augmentation during prolonged exposure therapy for PTSD led to greater symptom reduction and improved patient retention compared to a placebo, suggesting it may enhance treatment efficacy.

The study found that veterans who responded positively to hydrocortisone had higher glucocorticoid sensitivity before treatment, indicating that measuring glucocorticoid responsiveness could help identify patients who might benefit most from this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortisol augmentation of a psychological treatment for warfighters with posttraumatic stress disorder: Randomized trial showing improved treatment retention and outcome. Yehuda, R., Bierer, LM., Pratchett, LC., et al.[2022]

In a trial involving women with chronic PTSD, the CRHR1 antagonist GSK561679 did not show significant improvement compared to placebo, highlighting the challenge of achieving drug efficacy in the presence of strong placebo effects.

A substantial placebo effect was observed, with effect sizes up to 1.5 standard deviations, indicating that the structure and support of the clinical trial itself may have contributed to improvements in PTSD symptoms and cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo Effects Across Self-Report, Clinician Rating, and Objective Performance Tasks Among Women With Post-Traumatic Stress Disorder: Investigation of Placebo Response in a Pharmacological Treatment Study of Post-Traumatic Stress Disorder. Hodgins, GE., Blommel, JG., Dunlop, BW., et al.[2022]

A 10-day low-dose course of hydrocortisone (20 mg twice daily) significantly reduced PTSD and depression symptoms in 64 traumatic injury patients compared to a placebo, indicating its potential efficacy in preventing post-traumatic stress disorder.

Patients who had never received prior mental health treatment showed the greatest benefits, suggesting that hydrocortisone may be especially effective for those without a history of significant psychological issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of initial hydrocortisone administration at preventing posttraumatic distress in adult trauma patients: a randomized trial. Delahanty, DL., Gabert-Quillen, C., Ostrowski, SA., et al.[2021]

A single intravenous dose of hydrocortisone given within 6 hours after a traumatic event did not significantly reduce the incidence of PTSD compared to a placebo in a study of 118 patients.

However, administering hydrocortisone at night, when cortisol levels are naturally lower, showed a potential reduction in PTSD prevalence, indicating a need for further research in this specific timing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrocortisone in the emergency department: a prospective, double-blind, randomized, controlled posttraumatic stress disorder study. Hydrocortisone during golden hours. Carmi, L., Zohar, J., Weissman, T., et al.[2022]

Hydrocortisone significantly reduces PTSD symptoms and incidence compared to placebo, based on a meta-analysis of 8 studies involving 362 participants, with a strong effect observed when used preventatively.

While hydrocortisone shows promise as a low-cost treatment for preventing PTSD, the limited number of studies and their methodological quality highlight the need for more rigorous research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrocortisone administration for reducing post-traumatic stress symptoms: A systematic review and meta-analysis. Kothgassner, OD., Pellegrini, M., Goreis, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5981864/

The efficacy of initial hydrocortisone administration at ... Hydrocortisone recipients (n = 8–10) reported significantly fewer PTSD symptoms than did placebo control patients (n = 7–9) at 2-week and 1- and 3-month follow- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04924166

NCT04924166 | PTSD Prevention Using Oral Hydrocortisone This randomized control trial proposes to test a one-time prophylactic treatment for the prevention of symptoms of PTSD and related mental health disturbances.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33626392/

Hydrocortisone administration for reducing post-traumatic ... Conclusion: Hydrocortisone appears to be a promising and efficient low-cost medication for the prevention of PTSD. However, the small number of included ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00597857

Prevention of Posttraumatic Stress Disorder (PTSD) With ... The proposed research is designed to examine the efficacy of hydrocortisone (commercially-available cortisol) in preventing post-traumatic stress in a small- ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S016503271500364X

Dexamethasone-suppressed cortisol awakening response ... A more suppressed cortisol curve after dexamethasone significantly predicted greater PTSD symptom decrease in trauma-focused psychotherapy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02402114

Hydrocortisone for Prevention of Post-Traumatic Stress ... Early research has suggested that enhancing the body's natural cortisol response to a stressful event may be a safe and effective way of moderating the process ...

7. elsevier.health elsevier.health/en-US/preview/hydrocortisone

Hydrocortisone For the systemic treatment of severe inflammatory dermatoses, like severe exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, ...