REVERSE: Improving Treatment-resistant Post Traumatic Stress Disorder (PTSD) with Glucocorticoid Receptor (GR) Antagonism

Launched by CHRISTIAAN VINKERS · Nov 13, 2024

Keywords

ClinConnect Summary

The REVERSE clinical trial is investigating a new treatment for people with post-traumatic stress disorder (PTSD) who have not responded to standard therapies. The study focuses on a medication called mifepristone, which may help reduce PTSD symptoms by blocking the effects of cortisol, a stress hormone that can worsen PTSD. Participants in this trial will be randomly assigned to receive either mifepristone or a placebo (a dummy treatment) for 7 days. The trial aims to see if those taking mifepristone experience a significant decrease in their PTSD symptoms compared to those taking the placebo.

To be eligible for the trial, participants must be at least 18 years old, fluent in Dutch, and have been diagnosed with treatment-resistant PTSD, which means they haven’t improved after trying at least two approved treatments, including trauma-focused therapy. Participants will attend four meetings over 12 weeks, during which they will complete questionnaires and undergo clinical interviews to measure their symptoms and overall well-being. It's important to note that women of childbearing potential must agree to use non-hormonal contraception during the trial. The trial is currently recruiting, and all participation will be closely monitored to ensure safety and support.

Gender

ALL

Eligibility 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).