Glucocorticoid Receptor Antagonist for PTSD

(SEVEN Trial)

Recruiting at 1 trial location

Overseen By Stephanie Menjivar Quijano, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: SSRIs, SNRIs, Trazodone, Opiates

Must not be taking: Tricyclics, Lithium, Antipsychotics, Corticosteroids

Disqualifiers: Alcohol, Substance use, Bipolar, others

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

Compensation: Varies

Number of Visits: 8

Duration: 1 week

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, CORT108297, a glucocorticoid receptor antagonist, to determine its effectiveness in treating PTSD in Veterans. The drug blocks cortisol, a hormone that influences stress levels. Participants will receive either the actual drug or a placebo (a pill with no active ingredient) for seven days to compare results. Veterans with PTSD symptoms who have been stable on certain medications or therapies might be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

You may need to stop certain medications, like some antidepressants, mood stabilizers, antipsychotics, and corticosteroids, as they are not allowed in the trial. However, if you are on a stable dose of SSRIs, SNRIs, trazodone, or opiate pain medications, you can continue taking them. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CORT108297 is being tested for its safety in treating PTSD. In earlier studies, participants took 180 mg of CORT108297 daily for 7 days. Researchers have carefully monitored these studies to ensure participant safety.

While specific safety details are not provided here, early trials focus on how well people tolerate the treatment. If a treatment reaches this stage, it has demonstrated some safety in earlier research. This suggests that CORT108297 is likely safe enough for continued testing in people.

Researchers usually monitor participants for any side effects. This helps them learn about the treatment's safety and any possible risks. For those considering joining a trial, speaking with the study team can provide more personalized information. ^{1 2 3 4 5}

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

Most treatments for PTSD typically involve antidepressants or therapy, which can take weeks to show results. But CORT108297 works differently, targeting the glucocorticoid receptor, which may play a key role in the body's stress response. Researchers are excited about this treatment because it has the potential to show effectiveness in just seven days, making it a faster-acting option for individuals struggling with PTSD. Additionally, CORT108297 represents a new approach by directly interfering with stress hormone pathways, potentially offering relief for those who do not respond well to traditional treatments.

What evidence suggests that CORT108297 might be an effective treatment for PTSD?

Research shows that CORT108297, which participants in this trial may receive, might help treat PTSD by blocking certain receptors involved in stress. This could reduce PTSD symptoms by lowering the effects of stress hormones like cortisol. Early studies suggest this method might ease symptoms in people with PTSD. Although specific data on its effectiveness is still being collected, its mechanism offers a promising basis for potential benefits. ^{4 5 6 7 8}

Who Is on the Research Team?

Thomas C. Neylan, MD

Principal Investigator

San Francisco VA Medical Center, San Francisco, CA

Are You a Good Fit for This Trial?

This trial is for US veterans with PTSD from military service, including combat or sexual trauma. They must have had symptoms for over 3 months and agree to use two forms of contraception if applicable. Participants can be on stable doses of certain medications like trazodone or SSRIs/SNRIs but not others that affect the study drug's metabolism or increase suicide risk.

Inclusion Criteria

Criterion A event meets DSM-5 criteria and occurred during military service, including combat and military sexual trauma

I have been on a stable dose of medication for PTSD for at least 8 weeks.

I agree to use two reliable birth control methods, including a barrier method.

Exclusion Criteria

You have been diagnosed with alcohol, marijuana, or drug addiction in the last 3 months according to the DSM-5 guidelines.

I am not taking certain antidepressants, mood stabilizers, antipsychotics, or benzodiazepines.

You have experienced any kind of injury or accident within the past 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive CORT108297 or placebo for 7 days

1 week

Several visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Visits at day 7, 28, and 56

What Are the Treatments Tested in This Trial?

Interventions

• CORT108297
• Placebo

Trial Overview The trial is testing CORT108297, a new medication that blocks cortisol without affecting progesterone, which could help treat PTSD. It compares this drug to a placebo (a substance with no active drug). The goal is to see if it's effective and safe for treating PTSD in veterans.

How Is the Trial Designed?

Group I: CORT108297 Experimental Treatment 1 Intervention

CORT108297- 180mg daily for 7 days

Group II: Placebo Placebo Group 1 Intervention

Placebo- 180mg daily for 7 days

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

A double-blind, placebo-controlled trial involving 62 participants with and without PTSD showed that dexamethasone administration significantly improved fear extinction and safety discrimination in individuals with PTSD, reversing deficits seen in the placebo condition.

Dexamethasone appears to effectively suppress hyperactivity of the HPA axis, which is linked to exaggerated fear responses in PTSD, suggesting it could be a promising new treatment for reducing fear expression in affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study. Michopoulos, V., Norrholm, SD., Stevens, JS., et al.[2021]

This Phase II trial is evaluating the efficacy and safety of GSK561679, a novel CRH type 1 receptor antagonist, in treating PTSD in untreated adult women aged 18 to 65, over a six-week period.

The study aims to demonstrate that GSK561679 significantly reduces PTSD symptoms compared to placebo, while also exploring biological markers and neuropsychological performance to better understand the mechanisms behind PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a corticotropin releasing hormone type 1 receptor antagonist in women with posttraumatic stress disorder: study protocol for a randomized controlled trial. Dunlop, BW., Rothbaum, BO., Binder, EB., et al.[2022]

Individuals with current PTSD show significantly reduced glucocorticoid receptor (GR) hormone-binding potential in their blood cells compared to those with a history of trauma but without PTSD, indicating a specific alteration related to PTSD rather than trauma exposure itself.

Resilience to PTSD is linked to a higher proportion of glucocorticoid receptors capable of binding hormones, suggesting that receptor functionality may play a role in an individual's ability to cope with trauma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphocyte glucocorticoid receptor expression level and hormone-binding properties differ between war trauma-exposed men with and without PTSD. Matić, G., Milutinović, DV., Nestorov, J., et al.[2015]

In a study involving 12 PTSD patients and 12 healthy individuals, the antimineralocorticoid spironolactone was found to significantly increase basal cortisol and ACTH levels, suggesting that mineralocorticoid receptor activity is intact in PTSD patients.

The findings indicate that while mineralocorticoid receptor function is not enhanced in PTSD, the study could not rule out other compensatory factors that might influence cortisol output.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mineralocorticoid receptor function in patients with posttraumatic stress disorder. Kellner, M., Baker, DG., Yassouridis, A., et al.[2015]

High-dose glucocorticoid treatment (corticosterone) administered after fear conditioning in rats effectively reduced the return of fear, suggesting it may help prevent fear renewal after exposure therapy for anxiety disorders like PTSD.

The study found that this treatment decreased anxiety-like behavior without affecting the actual fear responses, indicating that glucocorticoids may work by reducing anxiety rather than altering how fear memories are formed or recalled.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose corticosterone after fear conditioning selectively suppresses fear renewal by reducing anxiety-like response. Wang, H., Xing, X., Liang, J., et al.[2014]

In a study involving 90 individuals with PTSD, both hydrocortisone (HC) and D-Cycloserine (DCS) were found to enhance fear extinction learning, as indicated by reduced skin conductance responses during extinction learning compared to a placebo.

These findings suggest that pharmacological agents like glucocorticoids and NMDA receptor agonists could be promising adjuncts to prolonged exposure therapy for improving treatment outcomes in PTSD, although further clinical implications need to be explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled experimental study of hydrocortisone and D-cycloserine effects on fear extinction in PTSD. Inslicht, SS., Niles, AN., Metzler, TJ., et al.[2022]

Early administration of the glucocorticoid receptor antagonist RU486 after a traumatic event in a rodent model of PTSD significantly reduces anxiety and fear-related behaviors, suggesting it may help correct stress-induced cognitive abnormalities.

The study indicates that early intervention with RU486 can reverse dysregulation in the glucocorticoid system, including normalizing plasma corticosterone levels and preventing overexpression of stress-related proteins in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of RU486 in Treatment of Traumatic Stress-Induced Glucocorticoid Dysregulation and Fear-Related Abnormalities: Early versus Late Intervention. Lin, CC., Cheng, PY., Hsiao, M., et al.[2022]

In a study involving 22 participants (11 with PTSD and 11 healthy controls), the mineralocorticoid receptor agonist fludrocortisone significantly reduced levels of ACTH and cortisol compared to placebo, indicating its potential effects on HPA axis activity.

Despite the observed differences in cortisol responses between PTSD subjects and controls after metyrapone treatment, the study found no evidence of altered mineralocorticoid receptor function in individuals with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mineralocorticoid receptor function in posttraumatic stress disorder after pretreatment with metyrapone. Otte, C., Muhtz, C., Daneshkhah, S., et al.[2013]

In a study of 15 male Vietnam veterans with PTSD compared to 11 normal subjects, those with PTSD had significantly higher levels of glucocorticoid receptors, suggesting a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.

Despite the increased number of glucocorticoid receptors in PTSD patients, cortisol levels were similar to those of normal subjects, indicating that receptor changes may contribute to PTSD symptoms without affecting cortisol production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphocyte glucocorticoid receptor number in posttraumatic stress disorder. Yehuda, R., Lowy, MT., Southwick, SM., et al.[2013]

Pre-stress administration of corticosterone (3 mg/kg/day) effectively reduces exaggerated startle responses and promotes body weight growth in a rat model of stress, lasting up to 21 days after stress cessation, indicating its potential as a preventive treatment for PTSD symptoms.

In contrast, lower doses of corticosterone (0.3 mg/kg/day) and post-stress administration were ineffective, highlighting the importance of timing and dosage in the therapeutic use of corticosterone for managing stress-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosterone mitigates the stress response in an animal model of PTSD. Jia, M., Smerin, SE., Zhang, L., et al.[2014]

In a study of 460 PTSD patients and 1158 control subjects, specific glucocorticoid receptor (GR) gene polymorphisms were found to interact with stressful life events and social support, significantly increasing the risk of developing PTSD.

Individuals with a combination of high traumatic events, certain GR gene variants, high levels of stress, and low social support had over three times the risk of developing PTSD, highlighting the importance of both genetic and environmental factors in PTSD susceptibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between glucocorticoid receptor polymorphisms, stressful life events, social support, and post-traumatic stress disorder. Lian, Y., Xiao, J., Wang, Q., et al.[2021]

Citations

1. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04452500

Post-Traumatic Stress Disorder - UCSF Clinical Trials The purpose of this study is to test the drug CORT108297, which blocks the hormone cortisol, for treatment of PTSD in Veterans, and establish a safety profile.

2. trialx.com trialx.com/clinical-trials/listings/268434/phase-iia-trial-of-a-selective-glucocorticoid-receptor-antagonist-in-the-treatment-of-veterans-with-posttraumatic-stress-disorder-ptsd-seven-study/

Phase IIa Trial of a Selective Glucocorticoid Receptor ... This is a randomized, double-blind, placebo-controlled Phase IIa clinical trial to test the efficacy and safety of CORT108297- 180mg daily for 7 days for PTSD ...

3. withpower.com withpower.com/trial/phase-3-stress-disorders-traumatic-8-2021-bd355

Glucocorticoid Receptor Antagonist for PTSD (SEVEN Trial) CORT108297 is unique because it works by blocking glucocorticoid receptors, which are involved in the body's stress response, potentially helping to reduce PTSD ...

4. va.gov va.gov/tuscaloosa-health-care/research/

Research | VA Tuscaloosa Health Care | Veterans Affairs 1. Studies in Post-traumatic Stress Disorder (PTSD) · Evaluates CORT108297 taken daily for 7 days. · Veterans age ≤69 with current PTSD symptoms ...

5. go.drugbank.com go.drugbank.com/conditions/DBCOND0038601

Post Traumatic Stress Disorder (PTSD) (DBCOND0038601) Effectiveness of Sana Treatment in Post-Traumatic Stress Disorder (PTSD) ... Improving Effectiveness: Treatment Outcome Research, No drug interventions ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04452500

Phase IIa Trial of a Selective Glucocorticoid Receptor ... This is a randomized, double-blind, placebo-controlled Phase IIa clinical trial to test the efficacy and safety of CORT108297- 180mg daily for 7 days for PTSD ...

7. reporter.nih.gov reporter.nih.gov/search/I_bJWIRR_0Kb3TKRVha0zw/project-details/11044036

RePORT RePORTER - National Institutes of Health (NIH) | We propose a two-site parallel group, randomized, double-blind, placebo-controlled Phase IIa clinical trial to test the efficacy and safety of CORT108297- 180mg ...

8. reporter.nih.gov reporter.nih.gov/search/ppHJaB7bx0u5x2c2xoNrgQ/project-details/11044036

Phase IIa Trial of a Selective Glucocorticoid ... - NIH RePORTER We propose a two-site parallel group, randomized, double-blind, placebo-controlled Phase IIa clinical trial to test the efficacy and safety of CORT108297- 180mg ...