Condition category
Mental and Behavioural Disorders
Date applied
17/06/2019
Date assigned
18/06/2019
Last edited
19/06/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
A substantial group of people with schizophrenia have experienced traumas in their lifetime and suffer from psychological complaints as a result of these traumas. Examples of these complaints are flashbacks, nightmares, avoidance of places and people related to the trauma, avoidance of thoughts and feelings related to the trauma, feeling strong negative emotions, and being more alert and vigilant than usual. This study investigates whether three trauma-focused treatments help to reduce these symptoms in people with schizophrenia. The treatments being investigated are Prolonged Exposure therapy (PE), Eye-movement Desensitization and Reprocessing (EMDR), and Cognitive Restructuring therapy (CR). PE and EMDR therapy aim to alleviate trauma-related complaints by encouraging the reprocessing of traumatic memories. In PE therapy, the therapist asks the participant to describe the traumas in a very detailed and vivid way while recording it. The participant listens to the recording at home. These exercises teach the participant that he or she can handle talking about the trauma and encourages the processing of the trauma. In EMDR therapy, the therapist asks the participant to talk about the trauma while the therapist moves his or her fingers from left to right in front of the eyes of the participant. The participant follows the fingers of the therapists with his or her eyes, thereby stimulating the processing of the trauma. CR works by changing negative trauma-related cognitions. In CR the therapist helps the participant to recognize negative trauma-related thoughts about the self, others and the world. Together, the participant and the therapist work to change these thoughts into more adaptive and tolerable thoughts. All three treatments consist of 16 sessions of 90 minutes over 10 weeks time.

Who can participate?
Adults with a psychotic disorder in the schizophrenia spectrum and post-traumatic stress disorder

What does the study involve?
Participants are randomly allocated into one of four groups: the PE group, the EMDR group, the CR group or the waiting-list group. Participants in the waiting list group receive a trauma-focused treatment of choice after 6 months. To measure if the treatments have an effect on the trauma-related complaints, participants participate in a set list of interviews and questionnaires before they start the treatment, after 8 sessions of treatment, after the last session of the treatment, and 3, 9 and 21 months after the last session. These interviews are carried out at the clinic where the participants receive their treatment.

What are the possible benefits and risks of participating?
The aimed for benefit of the three treatments is a reduction of trauma-related complaints. The treatments have been investigated in people with PTSD and schizophrenia before and have been shown to be safe and effective in reducing trauma-related complaints. The medical ethical committee has judged the study as inducing "no increased risk" for participants.

Where is the study run from?
1. Parnassia, Den Haag, Netherlands
2. Arkin, Amsterdam, Netherlands
3. Antes, Rotterdam, Netherlands
4. GGz Noord-Holland Noord, Netherlands
5. GGz Centraal, Hilversum, Netherlands
6. PsyQ, Den Haag, Netherlands
7. GGz Eindhoven, Eindhoven, Netherlands
8. GGz Oost-Brabant, Boekol, Netherlands

When is the study starting and how long is it expected to run for?
January 2018 to December 2023

Who is funding the study?
Stichting tot Steun VCVGZ (Foundation for VCVGZ Support), Netherlands

Who is the main contact?
1. Dr David van den Berg (scientific contact)
d.p.g.vander.berg@vu.nl
2. Simone Burger
s.r.burger@vu.nl

Trial website

Contact information

Type

Scientific

Primary contact

Dr David van den Berg

ORCID ID

http://orcid.org/0000-0002-8797-8217

Contact details

Van der Boechorststraat 1
room 2B-81
Amsterdam
1081 BT
Netherlands
+31 (0)883576765
d.p.g.vanden.berg@vu.nl

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

NL66431.029.19

Study information

Scientific title

The effect of prolonged exposure, EMDR and cognitive restructuring on PTSD symptoms in patients with PTSD and psychosis: a multicenter randomised controlled trial

Acronym

RE.PROCESS

Study hypothesis

The primary objective is to determine the effects of a full treatment dose of PE, EMDR, cognitive restructuring (CR), and Waiting List (WL) on researcher-rated severity of PTSD symptoms. The secondary objective is to investigate the effects of these treatments on researcher-rated presence of PTSD diagnosis, self-rated severity of PTSD, severity of complex PTSD symptoms, post-traumatic cognitions, dissociation, depression, paranoia, auditory verbal hallucinations, social functioning, disruption of social functioning by PTSD symptoms, resilience, personal recovery, sexual functioning, adversities, and revictimization. Third, with the 24-month follow-up the aim is to test the long-term effects on all the outcomes for the first time. Fourth, the study aims to explore how post-traumatic stress and psychosis interact dynamically, how the experimental treatments influence these interactions, and what factors significantly predict treatment response. The fifth objective is to determine the cost-effectiveness of the interventions. Sixth, the researchers will conduct a process evaluation of the therapy process by conducting interviews to examine how participants experienced receiving trauma-focused treatment.

Ethics approval

Approved 27/03/2019, Medical Ethics Committee of VU Medical Centre Amsterdam (METc VUmc: Van der Boechorstraat 7, room H-443, PO Box 7057, 1007 MB Amsterdam, the Netherlands; Tel: +31 (0)20 44 45 58 5; Email: metc@vumc.nl), ref: 2019.046 NL66431.029.19

Study design

Single-blind multicenter randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Post-traumatic stress symptoms in patients with chronic post-traumatic stress disorder and a comorbid psychotic disorder in the schizophrenia spectrum

Intervention

Participants are randomly assigned to one of four arms. Randomization is conducted by the independent randomisation bureau of Parnassia Psychiatric Institute with the use of block randomisation with the randomisation software from www.randomizer.org. Research Randomizer (Version 4.0). The three experimental arms consist of Prolonged Exposure therapy (PE), Eye Movement Desensitization and Reprocessing (EMDR), and Cognitive Restructuring (CR) therapy. The control arm is a waiting list group up to the 6-month follow-up, after which they may choose to receive a trauma-focused treatment of choice.

All therapists will deliver PE, EMDR and CR and will be trained in all the protocols. Participants in the three treatment arms will receive a maximum of 16 sessions. Sessions will be held two times a week and will last 90 minutes.

The PE therapy will be delivered conforming to the protocol of Foa, Hembree and Rothbaum (2007). This protocol consists of imaginal exposure (whereby each session is audio recorded and participants listen to these recordings five times per week) and in vivo exposure (based on a list of avoided trauma-related stimuli).

EMDR will be delivered according to the standard 8-phase protocol by Shapiro, using the Dutch translation of the EMDR protocol. Eye movements will be applied as the default dual attention stimulus.

The CR therapy will be delivered based on the treatment program developed by Mueser, Rosenberg, Jankowski, Hablen and Monica (2004). This adapted cognitive restructuring treatment is based on cognitive models of PTSD that posit that appraisals of traumatic events, and subsequent attempts to cope with the associated negative affect, are the key factors in the development and maintenance of PTSD. The most important adaptation of this CR protocol is the exclusion of direct memory processing since the developers expected that direct trauma memory processing would be too difficult to tolerate for patients with severe mental illnesses. The treatment methods and materials are also adapted to accommodate some of the unique challenges of people with severe mental illness, e.g. cognitive impairments.

Intervention type

Behavioural

Phase

Drug names

Primary outcome measure

Researcher-rated changes in severity of PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). This will be measured at baseline, at 7 weeks (mid-treatment), 13 weeks (post-treatment), 6-month follow-up, 12-month follow-up, and 24-month follow-up.

Secondary outcome measures

1. Changes in the number of participants fulfilling the diagnostic criteria of PTSD - CAPS-5
2. Self-rated severity of PTSD symptoms, measured using PTSD Checklist for the DSM-5 (PCL5)
3. Severity of complex PTSD symptoms, measured using International Trauma Questionnaire (ITQ)
4. Posttraumatic cognitions, measured using Brief version of the Posttraumatic Cognitions Inventory (PTCI-9)
5. Dissociation, measured using Trait State Dissociation Questionnaire short version (TSDQ-s)
5. Depression symptoms, measured usingBeck Depression Inventory II (BDI-II)
6. Paranoia, measured using Green et al. Paranoid Thought Scales (GPTS)
7. Auditory verbal hallucinations, measured using Psychotic symptoms rating scales (PSYRATS) & Voice Impact Scale (VIS)
8. Disruption of social functioning by PTSD symptoms, measured using ITQ
9. Resilience, measured using Brief Resilience Scale (BRS)
10. Personal recovery, measured using Questionnaire about the Process of Recovery (QPR)
11. Sexual functioning, measured using Arizona Sexual Experience Scale (ASEX) & Sexual Autonomy Scale (SAS)
12. Social functioning measured with 2 items adapted from the Time Use Survey
13. Adversities measured using the 7-item TTIP Adverse Events Questionnaire
14. Revictimization, measured using Trauma and Life Events Checklist (TALE)
Measures 1-11 will be measured at baseline, at 7 weeks (mid-treatment), 13 weeks (post-treatment), 6-month follow-up, 12-month follow-up, and 24-month follow-up.
Measures 12-14 will be measured weekly from baseline until 6-month follow-up.

Overall trial start date

01/01/2018

Overall trial end date

31/12/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Age 16+ years
2. A lifetime diagnosis of a psychotic disorder in the schizophrenia spectrum, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5)
3. Full DSM-5 diagnostic criteria for chronic PTSD on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) with a minimum score ≥23
4. Willingness to undergo randomisation and a trauma-focused therapy

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

200

Participant exclusion criteria

1. Changes in antipsychotic or antidepressant medication regimen within 4 weeks before the inclusion interview assessment (to control for medication effects)
2. Insufficient competence in the Dutch language
3. Severe intellectual impairment, defined as an estimated IQ of 70 or less
4. Not being able to travel (or be accompanied) to the outpatient service
5. Not willing or able to learn to use a smartphone

Recruitment start date

24/06/2019

Recruitment end date

31/12/2021

Locations

Countries of recruitment

Netherlands

Trial participating centre

Parnassia
Zoutkeetsingel 40
Den Haag
2512 HN
Netherlands

Trial participating centre

Arkin
Tesselschadestraat 31
Amsterdam
1054 ET
Netherlands

Trial participating centre

Antes
Prins Constantijnweg 48
Rotterdam
3066 TA
Netherlands

Trial participating centre

GGz Noord-Holland Noord
Stationsplein 138
Heerhugowaard
1703 WC
Netherlands

Trial participating centre

GGz Centraal
Rembrandthof, Laan van de Heelmeesters 2
Hilversum
1211 MS
Netherlands

Trial participating centre

PsyQ
Lijnbaan 4
Den Haag
2512 VA
Netherlands

Trial participating centre

GGz Eindhoven
Doctor Poletlaan 40
Eindhoven
5626 ND
Netherlands

Trial participating centre

GGz Oost Brabant
Kluisstraat 2
Boekol
5427 EM
Netherlands

Sponsor information

Organisation

Vrije Universiteit Amsterdam

Sponsor details

Boelelaan 1105
Amsterdam
1081 HV
Netherlands
+31 (0)20 598 9898
servicedesk.fco@vu.nl

Sponsor type

University/education

Website

https://vu.nl/nl/index.aspx

Funders

Funder type

Charity

Funder name

Stichting tot Steun VCVGZ (Foundation for VCVGZ Support), Netherlands

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The researchers are planning to offer the protocol for publication soon. The results on all hypotheses - as described in the 'study hypothesis' section - will be published, unreservedly. The researchers aim to publish in high-impact peer-reviewed journals. The sponsor will have no influence on the publication of the results.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/06/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

19/06/2019: Uploaded protocol Version 2.0, 15 February 2019 (not peer reviewed). 18/06/2019: Trial's existence confirmed by ethics committee.