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

Q: Who can participate in NCT06689254?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

Q: How do I contact the trial site for NCT06689254?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Q: Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Q: Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

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

REVERSE: Improving Treatment-resistant Post Traumatic Stress Disorder (PTSD) with Glucocorticoid Receptor (GR) Antagonism (NCT06689254) is a Phase 2 interventional studying Treatment-resistant PTSD, sponsored by Christiaan Vinkers. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

Rationale: Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop in people who have experienced or witnessed a traumatic event. Symptoms of PTSD include flashbacks, nightmares, difficulty sleeping, difficulty concentrating, irritability, and avoidance of people, places, or activities that remind the person of the traumatic event. Even though there are effective treatments (e.g. exposure-based psychotherapies and antidepressants), not all patients respond. Glucocorticoid receptor (GR) antagonism is a potential therapy for the treatment of treatment-resistant post traumatic stress disorder (PTSD) based on the idea that PTSD may be caused or exacerbated by dysregulation of the body's stress response system, and on the results of several small clinical trials. By blocking the actions of cortisol at the GR, it is thought that GR antagonists may be able to reduce the severity of PTSD symptoms and improve treatment outcomes. Randomized controlled trials (RCT) can provide high-quality evidence on treatment efficacy, and optimize evidence-based selection of off-label treatments for patients. Therefore the aim is to investigate whether the psychological and biological sequelae of traumatic stress and PTSD can be targeted by blocking the glucocorticoid receptor (GR) using the generic drug mifepristone in a double blind, placebo controlled RCT. Objective: To test the hypothesis that treatment with the GR-antagonist mifepristone is more effective than placebo to reduce PTSD symptom severity in treatment-resistant PTSD. Main trial endpoints: Improvement of PTSD symptoms, as measured with the monthly version of the CAPS-5 (Clinician Administered PTSD scale) in patients with treatment-resistant PTSD, 4 weeks after the start of the intervention. Secondary trial endpoints * PTSD symptom severity as measured with the weekly version of the PCL-5, from baseline till 12 weeks after the start of the intervention (T3). * Long-term PTSD symptom severity as measured with the CAPS-5, at 12 weeks after the start of the intervention (T3). * Loss of diagnosis (score of \<26 and absence of PTSD criteria with CAPS-5), 4 weeks after the start of the intervention. * Treatment response (minimum decrease of 10 point on the PCL-5 and CAPS-5 scores) at 1, 4 and 12 weeks after the start of the intervention. * Other clinical outcomes 1, 4, and 12 weeks after the start the intervention: * disability (WHO Disability Schedule 2.0; WHO-DAS II), * sleep (Insomnia Severity Index; ISI), * subjective stress (Perceived Stress Scale; PSS), * anxiety symptoms (Beck Anxiety Inventory; BAI), * depressive symptoms (IDS-SR), * suicidal ideation and behaviour (Columbia-Suicide Severity Rating Scale). Trial design: The experimental protocol consists of a placebo-controlled double-blind RCT with 4 face-to-face meetings: * baseline (T0, 2,5 hrs); * post-intervention T1, 8 days after start (1hr); * post-intervention T2, 4 weeks after start (2hr). * post-intervention T3, 12 weeks (2hr). Trial population: 60 adult patients (male/female, 18+ years), with treatment-resistant PTSD (non-response to two evidence-based PTSD treatments, at least one of which is trauma-focused psychotherapy). Intervention Patients are randomized for treatment with the GR antagonist mifepristone (1200 mg/day for 7 days) or matching placebo (daily for 7 days). Study medication will be dispensed during the baseline measurement (T0), and taken once daily for 7 consecutive days. Clinical measurements consist of clinical interviews and questionnaires. During baseline visits a pregnancy test is conducted in woman of child bearing potential (WOCBP), and blood is drawn at T1 to assess mifepristone plasma levels. Ethical considerations relating to the clinical trial including the expected benefit to the individual subject or group of patients represented by the trial subjects as well as the nature and extent of burden and risks: Mifepristone has been clinically used for Cushing's syndrome (anti-glucocorticoid effects) and termination of pregnancy (anti-progesterone effects) for several decades. Mifepristone is generally well-tolerated, and several double-blind studies using the identical duration and dose have shown (7 days, 1200 mg) that the safety profile of mifepristone is comparable to that of placebo treatment, and study dropouts due to side effects were higher for placebo (1.6%) than for mifepristone (1.4%). The most common adverse events (AEs) were nausea, headache, dizziness, and a dry mouth and were comparable between the mifepristone and placebo groups. With regard to mifepristone's progesterone receptor activity and its indication for pregnancy termination, WOCBP who do not agree to use a non-hormonal contraceptive method (condom) during the intervention and up to 1 month after the intervention, are strictly excluded from participating in this study.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Treatment-resistant PTSD and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 60 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Treatment-resistant PTSD subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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).

Treatments Being Tested

DRUG

Mifepristone 1200 mg daily

Oral tablets

DRUG

Placebo

Oral tablet

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Amsterdam UMC, location VUmc

Amsterdam, North Holland, Netherlands

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06689254), the sponsor (Christiaan Vinkers), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06689254 clinical trial studying?

Who can participate in NCT06689254?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06689254?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06689254. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06689254. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.