Improving treatment-resistant PTSD with a glucocorticoid receptor blocker

REVERSE: a Randomized Controlled Trial (RCT) to Ameliorate Treatment-resistant Post Traumatic Stress Disorder (PTSD) with Glucocorticoid Receptor (GR) Antagonism

Phase 2 Interventional Amsterdam UMC, location VUmc · NCT06689254

This study is testing if a medication called mifepristone can help adults with treatment-resistant PTSD feel better by blocking the effects of stress hormones.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment60 (estimated)
Ages18 Years and up
SexAll
SponsorAmsterdam UMC, location VUmc Academic / other
Locations1 site (Amsterdam, North Holland)
Trial IDNCT06689254 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of mifepristone, a glucocorticoid receptor antagonist, to treat individuals with treatment-resistant post-traumatic stress disorder (PTSD). The study aims to determine if blocking cortisol's effects can alleviate PTSD symptoms in patients who have not responded to standard treatments. Participants will be randomly assigned to receive either mifepristone or a placebo, and their PTSD symptoms will be assessed using the CAPS-5 scale. The trial focuses on adults who have experienced significant trauma and have not benefited from previous evidence-based therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a DSM-5 diagnosis of treatment-resistant PTSD who have not responded to at least two evidence-based treatments.

Not a fit: Patients with bipolar disorder, psychotic disorders, or current substance dependence may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from treatment-resistant PTSD.

How similar studies have performed: Previous small clinical trials have suggested that glucocorticoid receptor antagonism may be effective, but this approach is still considered novel in the context of treatment-resistant PTSD.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Mastery of Dutch language
* Age of ≥ 18 years of age and able to give written IC
* Participant agrees to be randomized
* DSM-5 diagnosis of PTSD, confirmed with clinical interview (CAPS-5)
* Treatment-resistant PTSD

  * CAPS-5 score ≥ 30
  * Nonresponse to two evidence-based treatments for PTSD recommended by a recent clinical practice guidelines delivered with fidelity and at an effective dose, at least one of which is a full course of trauma-focused psychotherapy

Exclusion Criteria:

* Bipolar disorder, psychotic disorder, or current alcohol/drug dependence that requires clinical attention.
* Female participant being a WOCBP and who does not want to use a non-hormonal contraceptive method (condom) during the intervention period and up to 1 month after the intervention.
* Female participants that are pregnant or breastfeeding. Pregnancy is excluded using a negative highly sensitive pregnancy test before the first dose of the study medication during the baseline visit.
* Female participants that have a history of unexplained vaginal bleeding or endometrial changes.
* Chronic adrenal insufficiency.
* Current use of:

  * Medications containing CYP3A4-inhibitors, as an interaction of CYP3A4-inhibitors and mifepristone leads to higher mifepristone plasma levels and increases the chance of having side effects. This also includes the consumption of grapefruit juice during the intervention
  * Medications containing CYP3A4-inductors, as an interaction of CYP3A4-inductors and mifepristone leads to lower mifepristone plasma levels and decreases the chance of having a beneficial effect. This also includes the consumption of St John's worth/hypericum perforatum during the intervention.
  * Medications containing CYP3A4 substrates.
  * Medications containing CYP2C8/9 substrates.
  * Medications containing P-gp and BCRP transported drugs
  * Glucocorticoid antagonists within 1 week before possible start of trial treatment.
  * Systemic corticosteroids. Topical corticosteroid treatment are acceptable, with the exception of inhaled corticosteroids (inhalators).
  * Unstable drug dosages (e.g. tapering of antidepressants).

Where this trial is running

Amsterdam, North Holland

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Treatment-resistant PTSDPTSDGR-antagonismmifepristone
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.