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Trial registered on ANZCTR


Registration number
ACTRN12616000956404
Ethics application status
Approved
Date submitted
17/06/2016
Date registered
20/07/2016
Date last updated
9/11/2018
Date data sharing statement initially provided
9/11/2018
Date results information initially provided
9/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Internet-based intervention for Posttraumatic Stress Disorder (PTSD) in soldiers: Exploring mechanisms of treatment outcome.
Scientific title
Evaluation of an internet-based intervention for Posttraumatic Stress Disorder (PTSD) in soldiers of the German Armed Forces: A randomized controlled trial.
Secondary ID [1] 289487 0
None.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Posttraumatic Stress Disorder (PTSD) 299180 0
Condition category
Condition code
Mental Health 299189 299189 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Type of intervention: Therapist-guided internet-based intervention.
The intervention is delivered via an online platform.

Duration and general information:
Intervention and treatment procedure:
The internet-based intervention lasts 5 weeks and includes 10 structured writing assignments. Patients complete two assignments per week. Each assignment requires approximately 45 minutes of writing time.

Communication between patient and therapist takes place within a secure messaging system that is part of the online intervention platform. Participants receive standardized instructions for each of the writing tasks and written feedback after one working day from a trained psychotherapist (personally assigned) after eight of the ten writing tasks. Participants do not receive feedback after session 2 (biographical reconstruction) and after session 5 (moderate exposure).
The feedback consists of generic parts that are complemented by individual feedback tailored to the participants’ specific needs (e.g. recognition for disclosing experiences, encouragement for exposure to traumatic event, reinforcement and motivation).

Additionally, participants are able to contact the intervention team if technical support is required. For questions related to the treatment, patients can contact their personal therapist via e-mail (additional contact on demand). Requests will be answered within one working day.

Adherence:
Login of participants is monitored and participants are asked to determine a specific date at which they plan to work through the next assignment. If participants miss an intended date, the therapist receives an automatic notification and contacts the client via e-mail.

Assessment and evaluation:
Before and after the treatment, patients are invited for 3 (treatment group, n=50) or 4 (wait list control group, n=50) face-to-face diagnostic and assessment sessions at the German Army Hospital in Berlin. Trained research staff conducts structured clinical interviews (CAPS, M.I.N.I. and Mini-ICF-APP) with all patients before onset of the treatment. Furthermore, the diagnostic assessments include self-report questionnaires (e.g. PCL-5), psychophysiological measures (e.g. eye-tracking, heart rate) and an assessment of biomarkers (e.g. HPA-axis markers, cytokines and oxytocin). In addition, patients are asked to collect saliva samples for two consecutive weekdays after each assessment session. Saliva samples for cortisol analysis as well as heart rate measurements are also included in two of four exposure sessions (see below) and are guided by instructions via the online-platform.

Training of research staff and psychotherapists:
The research staff consists of four psychologists that receive practical training for conducting clinical interviews and all assessment procedures prior to the study onset. Specifically, training takes 3 days (8 hours each) and includes performance of clinical interviews (M.I.N.I., CAPS) and concrete instructions on how to apply assessments (heart rate, sleep EEG, eyetracking assessment).
Two experienced psychotherapists receive a 2-day-training (8 hours each) on how to use the online intervention platform and on how to implement the intervention protocol and to interact with participants.
The study team is accompanied by a military study physician who provides additional training for critical situations and population specific demands. Supervision is scheduled weekly.

Contents, aims and methods of the intervention in detail:
Biographical reconstruction (Session 1-3)
Topic: Essays on three life phases: 1) from birth to age of 10, 2) age of 11 to 18, 3) age of 18 until occurrence of the traumatic event(s)
Aim: Narrative reconstruction of own biography; identification of resources
Method: Written biographical reconstruction

Moderate Exposure (Session 4-7)
Topic: Repeated detailed description of the traumatic event(s)
Aim: Alteration of trauma memory
Method: Written trauma exposure

Cognitive Reappraisal (Session 8-10)
Topic: Supportive letter to younger self, coping with events in the future
Aim: Integration of traumatic event in biography, to gain a new perspective on the event (e.g., challenging dysfunctional automatic thinking, correction of unrealistic assumptions)
Method: Written cognitive restructuring
Intervention code [1] 295074 0
Treatment: Other
Intervention code [2] 295220 0
Behaviour
Comparator / control treatment
Type of intervention: Therapist-guided internet-based intervention

The wait list intervention group receives the same treatment as described after an initial waiting period of six weeks. Patients in this group are seen for the initial assessment and pass through one additional assessment before the beginning of the treatment phase. The treatment procedure hereafter is identical to the protocol above.

The healthy controls (n=50) only pass through the initial assessment, but do not receive any treatment or follow-up assessments.
Control group
Active

Outcomes
Primary outcome [1] 298671 0
PTSD symptom severity:
PCL-5 (dimensional measure for symptom severity)

Timepoint [1] 298671 0
Pre-Treatment (immediately before start of intervention)
2 times during the course of the treatment, i.e., after completion of „Biographical Reconstruction“ (after Session 3) and after completion of „Moderate Exposure“ (after Session 7)
Post-Treatment (immediately after completion of treatment)
3-months follow-up
12-months follow-up
Primary outcome [2] 298843 0
PTSD clinical status:
CAPS (DSM-5-based structured interview for categorical diagnostics)
Timepoint [2] 298843 0
Pre-Treatment (immediately before start of treatment)
Post-Treatment (immediately after completion of treatment)
3-months follow-up

Secondary outcome [1] 324911 0
Psychopathology:
PHQ - Patient Health Questionnaire
GAD-7 - Generalized Anxiety Disorder 7-item Scale
Timepoint [1] 324911 0
Pre-Treatment (immediately before start of treatment)
2 times during the course of the treatment, i.e., after completion of „Biographical Reconstruction“ (after Session 3) and after completion of „Moderate Exposure“ (after Session 7)
Post-Treatment (immediately after completion of treatment)
3-months follow-up
12-months follow-up
Secondary outcome [2] 324912 0
Quality of life:
SWLS - Satisfaction With Life Scale
Timepoint [2] 324912 0
Pre-Treatment (immediately before start of treatment)
Post-Treatment (immediately after completion of treatment)
3-months follow-up
12-months follow-up
Secondary outcome [3] 324913 0
Emotion regulation:
DERS - Difficulties in Emotion Regulation Scale
Timepoint [3] 324913 0
Pre-Treatment (immediately before start of treatment)
Post-Treatment (immediately after completion of treatment)
3-months follow-up
12-months follow-up
Secondary outcome [4] 324914 0
Posttraumatic Cognitions:
PTCI - Posttraumatic Cognition Inventory
Timepoint [4] 324914 0
Pre-Treatment (immediately before start of treatment)
Post-Treatment (immediately after completion of treatment)
3-months follow-up
12-months follow-up
Secondary outcome [5] 324915 0
Posttraumatic growth:
PTGI - Post Traumatic Growth Inventory
Timepoint [5] 324915 0
Pre-Treatment (immediately before start of treatment)
Post-Treatment (immediately after completion of treatment)
3-months follow-up
12-months follow-up
Secondary outcome [6] 324916 0
Social support:
CSS - Crisis Support Scale
Timepoint [6] 324916 0
Pre-Treatment (immediately before start of treatment)
Post-Treatment (immediately after completion of treatment)
3-months follow-up
12-months follow-up
Secondary outcome [7] 324917 0
Assessment of attention processes and trauma related attention bias:
An eye tracking assessment is conducted in order to assess attention processes and trauma related attention bias by using a mobile 250 Hz eye tracking system (Type RED250MOBILE, firm SensoMotoric Instruments) and its accompanying software i-View-REDm for data collection and analyses.
Participants are presented with a behavioral task of viewing trauma related and non-trauma related images and words next to emotional (disgusted, angry, and fearful) and neutral faces. Presentation of stimuli is conducted using a desktop monitor.
The assessment of attention processes and trauma related attention bias is based on the following measurements: a) initial fixation b) duration of initial fixation c) gaze movements.
Two additional assessments are conducted in order to control for confounding influences on attention processes and trauma related attention bias measurements. First, potential occurrence of acute dissociation during the task is assessed by application of a dissociation scale (“Dissoziations-Spannungs-Skala-akut” (DSS-akut, Stiglmayr et al., 2003)) after completion of the behavioral task.
Second, participants rate the presented stimuli with respect to valence and arousal (images and word), and presented emotion (faces), respectively (check of manipulation). The rating of the stimuli is not accompanied or rather recorded by the eye tracker.
Timepoint [7] 324917 0
Pre-Treatment (immediately before start of treatment)
Post-Treatment (immediately after completion of treatment)
3-months follow-up

Secondary outcome [8] 324919 0
Biomarkers of PTSD:
Cortisol (hair, saliva)
DHEA-S (saliva)
alpha-Amylase (saliva)
Oxytocin (blood)
Interleukin-6, TNF- alpha (blood)
Timepoint [8] 324919 0
Pre-Treatment (immediately before start of treatment; only salivary cortisol and alpha-amylase on two consecutive days)
2 times during treatment (only salivary cortisol and alpha-amylase), i.e., during first and last exposure session, that is, Session 4 (week 2) and Session 7 (week 4)
Post-Treatment (immediately after completion of treatment; only salivary cortisol and alpha-amylase on two consecutive days)
3-months follow-up (only salivary cortisol and alpha-amylase on two consecutive days)
Secondary outcome [9] 324920 0
Heart rate variability:
Heart rate monitor chest strap
The device is worn for a 5-minute baseline measurement at rest as well as during a computer-based 20-minute thought suppression task. Measurements during each of the two treatment sessions consist of a 5-minute baseline prior to writing and continuous measurement during the 45-minute writing session.
Timepoint [9] 324920 0
Pre-Treatment (immediately before start of treatment)
2 times during treatment, i.e., during first and last exposure session, that is, Session 4 (week 2) and Session 7 (week 4)
Post-Treatment (immediately after completion of treatment)
3-months follow-up
Secondary outcome [10] 324921 0
Work ability:
Mini-ICF-APP-interview
Timepoint [10] 324921 0
Pre-Treatment (immediately before start of treatment)
3-months follow-up

Eligibility
Key inclusion criteria
Treatment group/Waitlist control group:
German-speaking soldiers (active and out of duty) of the German Armed Forces suffering from Posttraumatic Stress Disorder (PTSD). Participants need to have access to the internet.

Healthy control group:
German-speaking soldiers of the German Armed Forces who have experienced a potentially traumatic event or who have never experienced a potentially traumatic event.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Treatment group/Waitlist control group:
Patients with schizophrenia, schizotypal and delusional disorders (ICD-10: F20-F29)
Suicidal patients
Patients with acute manic episode
Patients with acute substance abuse or dependence
Patients in concurrent psychotherapeutic treatment

Healthy controls group:
Subjects fulfill criteria of PTSD or any other mental disorder

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer software using a random number generator.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
None
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data will be analysed using both qualitative and quantitative (Hierarchical Linear Modelling) analysis strategies.
The sample size is based on a power analysis using a meta-analytically determined expected effect size of 0.7 for internet-based trauma-focused interventions (power = 95%, p<.05, two-tailed).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7968 0
Germany
State/province [1] 7968 0

Funding & Sponsors
Funding source category [1] 293856 0
Government body
Name [1] 293856 0
German Federal Ministry of Defense (Verteidigungsministerium)
Address [1] 293856 0
Bundesamt fuer Ausruestung, Informationstechnik u. Nutzung der Bundeswehr - BAAINBw U2.1
Mr. Christian Kockelmann
Ferdinand-Sauerbruch-Strasse 1
56073 Koblenz
Country [1] 293856 0
Germany
Primary sponsor type
University
Name
Freie Universitaet Berlin
Address
Department of Clinical-psychological intervention
Habelschwerdter Allee 45
14195 Berlin
Country
Germany
Secondary sponsor category [1] 292687 0
Individual
Name [1] 292687 0
Prof. Dr. Christine Knaevelsrud
Address [1] 292687 0
Freie Universitaet Berlin
Department of Clinical-psychological intervention
Habelschwerdter Allee 45
14195 Berlin
Country [1] 292687 0
Germany
Other collaborator category [1] 279040 0
Hospital
Name [1] 279040 0
German Armed Forces Centre of Military Mental Health, Berlin
Address [1] 279040 0
Mr. H. Rau
Study Physician
German Armed Forces Centre of Military Mental Health, Berlin

Bundeswehrkrankenhaus Berlin
Scharnhorststrasse 13
10115 Berlin
Country [1] 279040 0
Germany

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295277 0
Ethics committee of Freie Universitaet Berlin
Ethics committee address [1] 295277 0
Habelschwerdter Allee 45
14195 Berlin
Ethics committee country [1] 295277 0
Germany
Date submitted for ethics approval [1] 295277 0
02/09/2014
Approval date [1] 295277 0
23/10/2014
Ethics approval number [1] 295277 0
85/2014
Ethics committee name [2] 295278 0
Ethics committee of Freie Universitaet Berlin
Ethics committee address [2] 295278 0
Habelschwerdter Allee 45
14195 Berlin
Ethics committee country [2] 295278 0
Germany
Date submitted for ethics approval [2] 295278 0
02/05/2016
Approval date [2] 295278 0
02/06/2016
Ethics approval number [2] 295278 0
116/2016

Summary
Brief summary
Background:
Soldiers of the German Armed Forces are regularly confronted with intense physical and mental demands. Up to three percent develop PTSD but a significant proportion of soldiers with PTSD does not make use of conventional mental health services. Reasons include limited treatment capacities, concerns and barriers on the soldiers’ side and illness-related impairments. Internet-based interventions are less affected by these barriers and well established as an effective treatment approach for PTSD. This study seeks to investigate the acceptance, efficacy and the mechanisms of change of an online PTSD-intervention for military personnel.

Intervention:
The treatment protocol is a modified version of “Interapy” originally developed by Lange and colleagues. It is based upon the well-established cognitive behavioural intervention approaches of exposure and cognitive restructuring. Within this therapist-guided online writing therapy the patient receives structured writing tasks and individual feedback by a personal therapist.
The first 3 sessions consist of written biographical reconstruction. The next 4 writing assignments contain trauma exposure. The last 3 tasks aim at cognitive reappraisal of trauma-related dysfunctional beliefs.

Method:
Both treatment groups (intervention group and wait list/intervention group) are compared with regard to the primary and secondary outcomes (e.g. symptoms of PTSD, life satisfaction), predictors of treatment-success (e.g. social support, therapy expectations and therapeutic relationship) and indicators of mechanisms of change (e.g. hormone levels, attention bias, biomarkers and heart rate during exposure). The healthy control group acts as baseline comparison group and neither receives treatment nor follow-up assessments.

Questions of research
Quantitative:
(1) Efficacy of the intervention (quantitative outcome measures)
(2) Change of diagnosis (categorical outcome)
(3) Changes in psychophysiological markers and biomarkers over the course of treatment
Qualitative:
(1) Potential side effects of the intervention
Trial website
https://therapie.ptzbw.org/app/
Trial related presentations / publications
None.
Public notes
A short announcement of the study has been given in
Rau, H., Kowalski, J.T., Stein, M., Hoellmer, H., Siegel, S., Willmund, G.D. (2016). Aktuelle militaerpsychiatrische und –psychologische Forschung in der Bundeswehr. Wehrmedizinische Monatsschrift, 60, 15-18.

Contacts
Principal investigator
Name 66754 0
Prof Christine Knaevelsrud
Address 66754 0
Freie Universitaet Berlin
Department of Clinical-psychological intervention
Habelschwerdter Allee 45
14195 Berlin
Country 66754 0
Germany
Phone 66754 0
+49-30-83855736
Fax 66754 0
Email 66754 0
christine.knaevelsrud@fu-berlin.de
Contact person for public queries
Name 66755 0
Prof Christine Knaevelsrud
Address 66755 0
Freie Universitaet Berlin
Department of Clinical-psychological intervention
Habelschwerdter Allee 45
14195 Berlin

Country 66755 0
Germany
Phone 66755 0
+49-30-83855736
Fax 66755 0
Email 66755 0
christine.knaevelsrud@fu-berlin.de
Contact person for scientific queries
Name 66756 0
Prof Christine Knaevelsrud
Address 66756 0
Freie Universitaet Berlin
Department of Clinical-psychological intervention
Habelschwerdter Allee 45
14195 Berlin
Country 66756 0
Germany
Phone 66756 0
+49-30-83855736
Fax 66756 0
Email 66756 0
christine.knaevelsrud@fu-berlin.de

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Due to data-handling procedures of the responsible institution, the decision will be made upon request.
What supporting documents are/will be available?
Informed consent form
Ethical approval
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary