REVERSE: a randomized controlled trial (RCT) to ameliorate treatment-resistant Post Traumatic Stress Disorder (PTSD) with Glucocorticoid Receptor (GR) antagonism

2024-511042-39-00 Protocol REVERSE Therapeutic exploratory (Phase II) Ongoing, recruiting

Start 13 Nov 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites · Protocol REVERSE

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruiting
Participants planned 60
Countries 1
Sites 1

Post-traumatic stress disorder (PTSD)

To investigate whether mifepristone (7-day, 1200 mg/day) is more efficacious than placebo in reducing PTSD symptom severity (Clinician Administered PTSD scale, CAPS-5) in patients with treatment-resistant PTSD in a randomized controlled trial.

Key facts

Sponsor
Amsterdam UMC
Participant type
Patients
Age range
18-64 years
Gender
Male and Female
Therapeutic area
Psychiatry and Psychology [F] - Mental Disorders [F03]
Trial duration
13 Nov 2024 → ongoing
Decision date (initial)
2024-04-19
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To investigate whether mifepristone (7-day, 1200 mg/day) is more efficacious than placebo in reducing PTSD symptom severity (Clinician Administered PTSD scale, CAPS-5) in patients with treatment-resistant PTSD in a randomized controlled trial.

Conditions and MedDRA coding

Post-traumatic stress disorder (PTSD)

VersionLevelCodeTermSystem organ class
21.1 PT 10036316 Post-traumatic stress disorder 100000004873

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2020-003385-40 REStoring mood after Early life Trauma – Glucocorticoid Receptor (GR) blockade as disease-modifying treatment for depression with childhood trauma, Herstel van stemming na jeugdtrauma - Glucocorticoïde Receptor (GR) blokkade als gerichte behandeling voor depressie na jeugdtrauma, Herstel van stemming na jeugdtrauma - Glucocorticoïde Receptor (GR) blokkade als gerichte behandeling voor depressie na jeugdtrauma, Herstel van stemming na jeugdtrauma - Glucocorticoïde Receptor (GR) blokkade als gerichte behandeling voor depressie na jeugdtrauma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Mastery of Dutch language
  2. Age of ≥ 18 years of age and able to give written consent
  3. Participant agrees to be randomized
  4. DSM-5 diagnosis of PTSD, confirmed with clinical interview (CAPS-5)
  5. Treatment-resistant PTSD: CAPS-5 score ≥ 30 and 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 6

  1. Bipolar disorder, psychotic disorder, or current alcohol/drug dependence that requires clinical attention.
  2. 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.
  3. 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.
  4. Female participants that have a history of unexplained vaginal bleeding or endometrial changes.
  5. Chronic adrenal insufficiency.
  6. Current use of medications containing: CYP3A4-inhibitors/inductors/substrates, CYP2C8/9 substrates, P-gp and BCRP transported drugs, glucocorticoid antagonists, systemic corticosteroids or unstable drug dosages (tapering/titrating antidepressants).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. To investigate whether mifepristone (7-day, 1200 mg/day) is more efficacious than placebo in reducing PTSD symptom severity 4 weeks after the start of the intervention, as measured with the monthly version of the CAPS-5 (Clinician Administered PTSD scale) in patients with treatment-resistant PTSD.

Secondary endpoints 5

  1. 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).
  2. Long-term PTSD symptom severity as measured with the CAPS-5, at 12 weeks after the start of the intervention (T3).
  3. Loss of diagnosis (score of <26 and absence of PTSD criteria with CAPS-5), 4 weeks after the start of the intervention.
  4. 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.
  5. Other clinical outcomes 1, 4, and 12 weeks after the start the intervention: o disability (WHO Disability Schedule 2.0; WHO-DAS II), o sleep (Insomnia Severity Index; ISI), o subjective stress (Perceived Stress Scale; PSS), o anxiety symptoms (Beck Anxiety Inventory; BAI), o depressive symptoms (IDS-SR), o suicidal ideation and behaviour (Columbia-Suicide Severity Rating Scale).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Mifepristone

SUB08956MIG · Substance

Active substance
Mifepristone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
1200 mg milligram(s)
Max total dose
8400 mg milligram(s)
Max treatment duration
7 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo

SUB21402 · Substance

Active substance
Placebo
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
4 U unit(s)
Max total dose
28 U unit(s)
Max treatment duration
1 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

47 Total trials 24 Recruiting 20 Ended
Academic / Non-commercial
Sponsor organisation
Amsterdam UMC
Address
De Boelelaan 1117
City
Amsterdam
Postcode
1081 HV
Country
Netherlands

Scientific contact point

Organisation
Amsterdam UMC
Contact name
Felix Linsen

Public contact point

Organisation
Amsterdam UMC
Contact name
Felix Linsen

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ongoing, recruiting 60 1
Rest of world — 0 —

Investigational sites

Netherlands

1 site · Ongoing, recruiting
Amsterdam UMC
Psychiatry, De Boelelaan 1117, 1081 HV, Amsterdam

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Netherlands 2024-11-13 2025-03-07

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-511042-39 3
Protocol (for publication) D4_ Patient facing documents CTQ 1
Protocol (for publication) D4_ Patient facingdocuments AUDIT2 1
Protocol (for publication) D4_ Patient facingdocuments BAI 1
Protocol (for publication) D4_ Patient facingdocuments Bijwerkingen 1
Protocol (for publication) D4_ Patient facingdocuments Brief COPE-16 1
Protocol (for publication) D4_ Patient facingdocuments C-SSRS Since Last Month 1
Protocol (for publication) D4_ Patient facingdocuments C-SSRS-Since Last Visit 1
Protocol (for publication) D4_ Patient facingdocuments CAPS-5 1
Protocol (for publication) D4_ Patient facingdocuments Connor-Davidson RS-2 1
Protocol (for publication) D4_ Patient facingdocuments Contraindicaties Mifepriston 1
Protocol (for publication) D4_ Patient facingdocuments Demografie 1
Protocol (for publication) D4_ Patient facingdocuments Drugsgebruik 1
Protocol (for publication) D4_ Patient facingdocuments IDS-SR 1
Protocol (for publication) D4_ Patient facingdocuments IPAQ 1
Protocol (for publication) D4_ Patient facingdocuments ISI-5 1
Protocol (for publication) D4_ Patient facingdocuments LTE Brugha-Life events 1
Protocol (for publication) D4_ Patient facingdocuments MARS5 1
Protocol (for publication) D4_ Patient facingdocuments PCL-5 week 1
Protocol (for publication) D4_ Patient facingdocuments PSS 1
Protocol (for publication) D4_ Patient facingdocuments Roken 1
Protocol (for publication) D4_ Patient facingdocuments SSL-12 1
Protocol (for publication) D4_ Patient facingdocuments WHODAS 1
Protocol (for publication) D4_Patient facingdocuments Brief COPE-16 v2_clean 2
Protocol (for publication) D4_Patient facingdocuments Brief COPE-16 v2_tracked changes 2
Protocol (for publication) D4_Patient facingdocuments CAPS-5 v2_clean 2
Protocol (for publication) D4_Patient facingdocuments CAPS-5 v2_tracked changes 2
Recruitment arrangements (for publication) K1_Recruitment procedure 1
Recruitment arrangements (for publication) K2_ Recruitment material brochure 1
Recruitment arrangements (for publication) K2_ Recruitment material poster 1
Subject information and informed consent form (for publication) L1_SIS and ICF adults 1
Subject information and informed consent form (for publication) L1_SIS and ICF adults_clean 4
Subject information and informed consent form (for publication) L1_SIS and ICF adults_track changes 1
Subject information and informed consent form (for publication) L1_SIS and ICF adults_tracked changes 4
Subject information and informed consent form (for publication) L2_ Other subject information material pregnancy during participation 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Mifegyne NL 1
Synopsis of the protocol (for publication) D1_ Protocol synopsis 1

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-02-01 Netherlands Acceptable
2024-04-16
 2024-04-19
2 SUBSTANTIAL MODIFICATION SM-1 2024-05-21 Netherlands Acceptable 2024-06-28
3 SUBSTANTIAL MODIFICATION SM-2 2025-12-19 Netherlands Acceptable
2026-02-24
 2026-02-24

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