Study Setting and Funding
The study is conducted at the Division of Clinical Psychology and Psychotherapy and the Institute of Sports and Preventive Medicine at Saarland University, Germany. NET is offered at the Psychotherapeutic Outpatient Clinic of Saarland University. Medical diagnostic is performed at the Institute of Sports and Preventive Medicine at Saarland University. The location for MAET is variable, e.g. the running path is chosen close to each participants’ home. The present trial is funded by the German Research Foundation (DFG; Project number: 426361032) and registered in German Clinical Trials Register (DRKS) (DRKS ID: DRKS00022145).
Sample Size And Power Calculation
Sample size was calculated using G*Power 3.1.9.2. (Faul et al., 2009) to detect the interaction in a 2x2 ANOVA (group: NET+ vs. NET; time: pre vs. post) with a power of .80 (α = .025 because of two primary outcomes). Rosenbaum and colleagues (2015) provide evidence for a moderate adjuvant effect f = 0.25 of exercise (ηp2depression = .15; ηp2PTSD = .07) compared to usual care (including psychotherapy, pharmacotherapy, and group therapy). The a priori power calculation resulted in a total sample size of n = 68 assuming a moderate adjuvant effect and at least a small correlation between the test times (r = .15). To ensure statistical power, n = 34 participants per group will be recruited.
Recruitment And Eligibility Criteria
Multiple local social services and employment agencies are involved in the recruitment of participants. Participants are referred to participate by themselves, peers, counsellor and social workers, physicians, local refugee counselling centres and welfare organisations. To participate, the refugees need to be (1) member of a German health insurance (registration as a recognized refugee in Germany required). Further inclusion criteria are (2) a minimum age of 16 years, (3) the diagnosis of PTSD, and (4) clinically relevant depression symptoms. Participants indicate at least (5) one year (pre study) of no endurance training as well as (6) no experience of endurance training in the past (i.e., not more than one weekly unit of endurance sports during the last two years and no lifetime competitive practice in endurance sports).
Exclusion criteria are (1) cardiovascular diseases, serious deviations in Complete Blood Count (CBC) and further physical restrictions that preclude participation in moderate endurance training (e.g., serious systemic diseases, coronary stenosis with angina pectoris, cardiac insufficiency under resting conditions, severe cardiac arrhythmia, and acute illnesses, such as acute infections, severe electrolyte imbalance, recent heart attacks, heart wall aneurism). Furthermore, participants suffering from (2) eating disorders (due to the risk of abusing physical activity for weight loss), (3) acute psychosis, (4) acute suicidal behaviour or (5) enduring substance abuse disorders/ enduring drug and alcohol abuse are excluded. Additionally, (6) pregnancy and (7) the use of benzodiazepines leads to exclusion from the study. Participants that are currently treated with medication are not excluded from the study. However, the dosage and kind of medication is documented, and the treating physician (psychiatrist, general practitioner) is asked to keep the medication constant during the study period. In the final analyses the medication will be included as a covariate.
Procedure
Screening
A first check of inclusion and exclusion criteria is assessed during a personal interview/ phone call before the screening questionnaires are sent to potential participants. Due to the health recommendations in the context of the Covid − 19 pandemic, the screening questionnaires assessing PTSD symptoms, anxiety, depression, and general psychological distress (PCL-5, HSCL-25) are sent to potential participants by mail or email. Participants receive the screening questionnaires in their native language (Arabic, Persian, Tigrinya, Kurdish, English). A second copy (in German or English) is given to local assistants who support the participants in filling in the screening questionnaires. For illiterates the screening and diagnostic questionnaires is conducted as an interview supported by interpreters.
Initial Interview
Potential participants are invited to an initial interview, if they report psychological distress in the screening questionnaires. The initial interview is conducted by a licensed psychotherapist and serves to assess study eligibility. During the initial interview participants are informed about the study protocol neglecting the hypotheses of the trial. If the initial interview suggests participants’ study eligibility (suspected diagnosis of PTSD and depressive symptoms), participants are asked to provide informed consent and are invited to participate in detailed psychological and medical diagnostic sessions. Participants, who show signs of clinical distress, but are not eligible for study participation (e.g., other suspected diagnosis than PTSD) also receive a treatment offer at the Psychotherapeutic Outpatient Clinic of Saarland University.
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Psychological Assessment
The detailed psychological assessment includes structured interviews such as the Clinician-Administered PTSD Scale (CAPS; Weathers et al., 2013a), the Hamilton Depression Scale (HAM-D; Hamilton, 1960; 1967) and the Structured Clinical Interview for DSM-5 Clinician Version (SCID-5-CV; First et al., 2016), checklists such as the War and Adversity Exposure Checklist (WAEC; Ibrahim et al., 2018b) and self-report questionnaires assessing general mental distress (Brief Symptom Checklist (BSCL); Franke, 2017), sleep quality (Pittsburgh Sleep Quality Index (PSQI); Buysse et al., 1989) and agoraphobic symptoms and somatoform symptoms (Questionnaire on Body-Related Anxieties, Cognitions and Avoidance (Fragebogen zu körperbezogenen Ängsten, Kognitionen und Vermeidung; AKV); Ehlers et al., 2001). The same test battery (except of the SCID-5-CV) is completed by the participants again after the completion of treatment (T1) and at six-month follow-up (T2).
Medical Assessment
To assess participants’ physical eligibility a detailed medical diagnostic is performed (including evaluation of medical history, resting and stress Electrocardiogram (ECG), spiroergometry, Complete Blood Count (CBC)).
Randomization
Participants who meet the eligibility criteria are randomly assigned to the NET- or NET+-group after the diagnostic assessment.
NET and NET+
All participants receive 10 x 100 min of NET. The NET+-group additionally receive MAET. The total duration of the treatment is estimated to range from 10–15 weeks.
Language Mediation And Translation
Diagnostic psychotherapeutic sessions are accompanied by interpreters who are fluent in the participants’ native speech and in German. It is assumed that psychotherapy with the use of interpreters does not negatively influence the psychotherapy outcome (Miller et al., 2005; Brune et al., 2011). Each interpreter is informed about the rationale and procedure of NET in detail prior to the start of the first diagnostic session. During therapeutic sessions interpreters are instructed to take a neutral, passive role and solely translate everything the participant and psychotherapist are saying. All questionnaires are available in each participants’ native speech.
Transcription
NET sessions are transcribed by students who passively participate in the psychotherapeutic sessions. So, psychotherapists can fully concentrate on the participant.
Mental Hygiene
Every fourth therapy session, language mediators and co-writing students receive group supervision led by the head of the Psychotherapeutic Outpatient Clinic of Saarland University to prevent psychological distress (through the refugees' narratives). In addition, there is the possibility of individual supervision if required.
Randomization
The trial is conceptualized as a single blind design. Participants are a priori assigned to the NET+-group and NET-group via computer-assisted randomization using Mersenne Twister in IBM SPSS Statistics version 22.0 (IBM Corp, 2013). After having successfully completed the screening and the medical and psychological diagnostic, a closed envelope containing the group assignment is given to the participants.
Treatment Fidelity
All psychotherapists that participate in the current trial were trained in NET in a two-day online workshop led by Prof. Dr. Claudia Catani. Additionally, all psychotherapeutic sessions are audio recorded. The treatment fidelity is randomly monitored by an experienced psychotherapist.
Table 1
Session No.
|
Therapeutic Content
|
1
|
Exploratory sessions
|
Relationship-oriented
Assess of medication, suicidal behavior, risk of dissociation
Development of the emergency plan
Review of psychosocial problems
|
2
|
Psychoeducation on Trauma, PTSD, and memory
Rationale and basic principles of NET and trauma-focused therapy
Preparing for the following NET sessions
|
3
|
Narrative Exposure Therapy
|
Lifeline
|
4
|
Starting the narration at birth
In-sensu exposure of the first traumatic life-event
|
5–11
|
Rereading of the previous narration to add further details if necessary
Continuing the in-sensu exposure of further traumatic events following the narration
|
12
|
Rereading of the whole written narration/ relaying of the lifeline
Appreciating and signing the written narration
Optimistic perspective on future considered in a positive light
|
Notes. MAET starts in the third session together with the beginning of NET.
Intervention
Exploratory Sessions
The first part of the psychotherapeutic treatment consists of two exploratory sessions which are mandatory in the German health care system. During the exploratory sessions psychotherapists explore participants’ current situation and their symptomatology. They also assess current medication, suicidal behavior, and dissociation as well as develop an emergency plan. Further, the ethical principles (adapted to the Universal Declaration of Human Rights, UDHR) of NET, the effectiveness of NET and its risks and side effects, such as change in cognition, emotion and relationships, are addressed. Exploratory sessions also serve to clarify the role assignment of the persons (participant, psychotherapist, interpreter, co-writing students) involved in therapy. The aim of the exploratory sessions is also to initiate a good relationship between the psychotherapist and the participant. Moreover, the exploratory sessions are to discuss any outstanding questions. Table 1 provides an overview of the psychotherapeutic treatments summarizing the content of each psychotherapeutic session.
Psychoeducation
Psychoeducation includes the definition of trauma, trauma-associated consequences, fear structure, and emerging and maintaining factors of trauma memory and PTSD. In addition, the rationale, procedure, and effectiveness of NET will be explained in detail. The aim of the psychoeducation is to thoroughly inform participants about trauma, PTSD, and the rationale of trauma-focused therapy such as NET to enable them to make a self-determined decision for or against undergoing trauma exposure in-sensu.
Narrative Exposure Therapy
NET is a well-established, exposure-based psychotherapeutic intervention for the treatment of PTSD (e.g., Neuner et al., 2010; Lely et al., 2019). NET works through reprocessing and integrating challenging trauma-associated memories into a coherent narrative. In the present trial NET consists of 10 weekly sessions (each with a duration of 100 min). During the first NET session the participant’s lifeline is laid to get a chronological overview of the participants’ life and the experienced traumatic events. The lifeline includes a summary of participants’ relevant life events with life-threatening and traumatic events symbolized by stones and positive or happy major events symbolized by flowers. Further candles are used to acknowledge for situations of grief such as losses, social pain, or rejection (Elbert et al., 2015).
Each lifeline event is classified spatially and temporally and receives an individual headline. The following sessions consist of the in-sensu exposure for each traumatic event. To ensure an effective exposure the psychotherapist encourages participants to recall the traumatic events in emotion, in sensation, in cognition and in trauma-related physiological details. The exposure of a maximum of two traumatic events must be completed in one session. All events are documented in wording and chronology. In every following session, the latest event is briefly summarized and supplemented if necessary.
In the final session the events that constitutes the participant’s life are reviewed as a contextualized and integrated narration. In the case of multiple exposure to very similar traumatic events the participant’s lifeline is reconstructed instead of rereading the narrative with respect to the risk of dissolving the chronological order of narration. The participant, the psychotherapist, the co-writing student, and the interpreter sign the narrative, that is subsequently handed to the participant. The closing procedure serves to appreciate the participants’ life and to provide an optimistic perspective on the broader future visioned in a positive light.
Narrative
Written transcripts of each narrative exposure are provided by the co-writing students attending the therapy and are compiled into a holistic narrative. The exposed traumatic events are documented in the past tense and submitted weekly to the psychotherapist for revision. The participants are encouraged to revise and add to the narrative in each follow-up session and in the final NET session.
Implementation Of Narrative Exposure Therapy
The therapy takes place at the Psychotherapeutic Outpatient Clinic of Saarland University and is conducted by licensed psychotherapists or psychotherapists in initial training. The psychotherapists receive a professional NET coaching before starting the therapy and receive supervision by an experienced psychotherapist after every second double session.
Moderate-intensity Aerobic Exercise Training
Moderate-intensity Aerobic Exercise Training (MAET) in the present study is adapted to the national recommendation for the treatment of depression and training intervention designs recommended by WHO for health of adults aged between 18 and 64 (DGPPN, 2017; WHO, 2022). Current research examining the effect of monotherapeutic or adjunctive exercise provides empirical support for this recommendation (Hecksteden et al., 2013; Wegner et al., 2020). In addition to NET, the NET+-group receives three weekly sessions of MAET consisting of 45 minutes of jogging at 60% heart rate reserve (+/- 5 bpm), with one supervised and two unsupervised training sessions per week. To be included in the final analysis participants must complete 70% of MAET (i.e., 21 MAET sessions) (Hecksteden et al., 2013). If the participants’ performance in MAET drop below 21 MAET sessions, data at T1 and T2 will be imputed by Fully Conditional Specification (FCS; Sterne et al., 2009) (see Dealing with Missing Data). Each participant of the NET+-group receives a mobile heart rate monitor with integrated memory function (Sigma ID.Free) and a compatible heart rate belt (Sigma R1 ANT+/BLE + COMFORTEX) to control and record parameters such as duration (in min), route (in m), speed (in min/km), altitude (in m) and average heart rate (in bpm) during MAET. To control for variability in altitude, participants are instructed to keep the altitude of the MAET route at a minimum. To ensure an aerobic exercise training with moderate intensity, the heart rate monitor is programmed to display a green light when participant’s heart rate was in the individually predefined heart rate zone. In addition to the digital recording of the MAET, participants document the completed MAET session and their mood before and after MAET training in a diary.
Measurements
Table 2 provides on overview of all measures and assessment points.
Table 2
Assessments’ Characteristics and Schedule
Assessments and Measures
|
Evaluation
|
Schedule of Assessment
|
Outcome
|
|
|
T0
|
T1
|
T2
|
|
Sociodemographic details
|
Self-report
|
x
|
|
|
Additional
|
PCL-5
|
Self-report
|
x
|
x
|
x
|
2nd
|
HSCL-25
|
Self-report
|
x
|
x
|
x
|
2nd
|
CAPS
|
Interview
|
x
|
x
|
x
|
1st
|
WAEC
|
Interview
|
x
|
x
|
x
|
1st
|
HAM-D
|
Interview
|
x
|
x
|
x
|
1st
|
BSCL
|
Self-report
|
x
|
x
|
x
|
2nd
|
AKV
|
Self-report
|
x
|
x
|
x
|
2nd
|
PSQI
|
Self-report
|
x
|
x
|
x
|
2nd
|
SCID-5-CV
|
Interview
|
x
|
|
|
Additional
|
Medical history
|
Self-report,
Interview
|
x
|
|
|
Explorative
|
CBC
|
|
x
|
x
|
x
|
Explorative
|
Spiroergometry
|
|
x
|
x
|
x
|
Explorative
|
Submaximal parameters
|
|
x
|
x
|
x
|
Explorative
|
Resting ECG
|
|
x
|
x
|
x
|
Explorative
|
Stress ECG
|
|
x
|
x
|
x
|
Explorative
|
Motivation in MAET
|
Interview
|
|
x
|
|
Explorative
|
Notes. T0 = Baseline assessment before randomization and treatment; T1 = assessment after treatment completion; T2 = assessment at six month follow-up; PCL-5 = PTSD Checklist for DSM-5; HSCL-25 = Hopkins Symptom Checklist-25; CAPS = Clinician-Administered PTSD Scale; WAEC = War and Adversity Exposure Checklist; HAMD-D = Hamilton Depression Scale; BSCL = Brief Symptom Checklist; AKV = Questionnaire on Body-Related Anxieties, Cognitions and Avoidance (Fragebogen zu körperbezogenen Ängsten, Kognitionen und Vermeidung); PSQI = Pittsburgh Sleep Quality Index; SCID-5-CV = Structured Clinical Interview for DSM-5 Clinician Version; CBC = Complete Blood Count; ECG = Electrocardiogram; MAET = Moderate-intensity Aerobic Exercise Training.
Primary Outcomes
Posttraumatic Stress Disorder
PTSD-symptomatology are assessed with the PTSD Checklist for DSM-5 (PCL-5), the Clinician-Administered PTSD-Scale for DSM-5 (CAPS), and the War and Adversity Exposure Checklist (WAEC). All three measures are assessed before the start of the treatment (T0), post-treatment (T1) and at six-month follow-up (T2).
The PCL-5 is a 20 item self-report questionnaire assessing the 20 DSM-5 PTSD criteria on a five-point Likert scale ranging from 'not at all' to 'extremely'. A score higher than 33 is indicative of probable PTSD (Blevins et al., 2015; Krüger-Gottschalk et al., 2017; Nesterko et al., 2020). Previous studies in refugee samples reported Cronbach's \(\alpha\) from \(\alpha\) = .93 − .97 for different language versions (Ibrahim et al., 2018a, Nesterko et al., 2020). The questionnaire serves to screen for inclusion criteria and precedes the detailed assessment of PTSD symptoms.
PTSD symptom severity is assessed with the Clinician-Administered PTSD Scale for DSM-V (CAPS; Weathers et al., 2013a). The CAPS is a structured interview, which is the gold standard in the diagnosis of PTSD. The German version of the CAPS, which is translated by Interpreters during the interview, shows sound psychometric properties (Müller-Engelmann et al., 2020).
Experienced traumatic events are examined using the War and Adversity Exposure Checklist (WAEC; Ibrahim et al., 2018b), which consists of 26 items assessing different traumatic events. The WAEC combines items from various instruments that examine traumatic events such as the Life Events Checklist for DSM-5 (Weathers et al., 2013b) and the War Exposure Scale (Ibrahim et al., 2018b). The WAEC shows good internal consistency (Cronbach's \(\alpha\) = .88) (Ibrahim et al., 2019).
Depression
Depressive symptoms are assessed with the Hopkins Symptom Checklist-25 (HSCL-25) and the Hamilton Depression Scale (HAM-D). Depressive symptoms are assessed before treatment (T0), post-treatment (T1) and at six-month follow-up (T2).
The HSCL-25 (based on Derogatis et al., 1974) is a 25 item self-report questionnaire assessing depression (15 items) and anxiety (10 items) on two subscales. Each item is answered on a four-point Likert scale ranging from 'not at all' to 'extremely'. A subscore for depression, anxiety, and a total score (measuring general psychological distress due to anxiety and depression symptoms) can be determined. Both subscales and the total score show good internal consistencies with Cronbach's α = .84 − .94 (Glaesmer et al., 2014). The HSCL-25 has already been successfully implemented in a sample of refugees (Lavik et al., 1999) and asylum seekers (Jakobsen et al., 2011).
The HAM-D (Hamilton, 1960; 1967) is the most widely used clinician administered depression assessment scale, that is cross-culturally validated (Vindbjerg et al., 2019). The HAM-D has been used to examine depressive symptoms in refugees (e.g., Stenmark et al., 2013). The main part of the clinical interview consists of 17 items. Four further items have been added to the interview to assess subtype of depression. The assessment of mild depressive symptoms leads to inclusion.
Secondary Outcomes
Secondary outcomes are also assessed at T0, T1 and T2.
General Mental Distress
General mental distress is measured using the Brief Symptom Checklist (BSCL; Franke, 2017), the German version of the Brief Symptom Inventory (BSI; Derogatis & Melisaratos, 1983; Derogatis, 1993). The BSCL is a self-report questionnaire comprising 53 items on nine subscales (hostility/aggression, anxiety, depression, paranoia, phobic anxiety, psychotecism, somatisation, interpersonal sensitivity, and compulsivity). The global severity index shows Cronbach's α = .97 with the reliability of the subscales ranging from Cronbach's α = .72 for hostility and phobic anxiety to Cronbach's α = .88 for depression (Franke et al., 2019).
Agoraphobia and Somatoform Complaints
Agoraphobic symptoms and somatoform complaints are assessed with the Questionnaire on Body-Related Anxieties, Cognitions and Avoidance (Fragebogen zu körperbezogenen Ängsten, Kognitionen und Vermeidung AKV; Ehlers et al., 2001), a self-report measure, which is a compilation of the Body Sensations Questionnaire (BSQ; Chambless et al., 1984), the Agoraphobic Cognitions Questionnaire (ACQ; Chambless et al., 1984) and the Mobility Inventory (MI; Chambless et al., 1985). The ACQ consists of 14 items and measures dysfunctional cognitions in relation to potential catastrophic consequences arising from panic or anxiety on two subscales: loss of control and physical concerns. The BSQ comprises 17 items on a five-point scale from 1 = 'not at all' to 5 = 'extremely'. The MI assesses self-reported agoraphobic avoidance behavior in 27 situations. The internal consistencies of the subscales vary from sufficient reliability of Cronbach's α = .78 (ACQ) to Cronbach's α = .88 and very good reliability Cronbach's α = .94 (MI, avoidance behavior alone) (Geue et al., 2016).
Sleep Quality
The Pittsburgh Sleep Quality Index (PSQI; Buysse et al., 1989) is a self-report measure assessing sleep quality and sleep disturbances over the past month. It consists of 19 items assessing sleep quality, sleep latency, sleep duration, sleep efficiency and sleep disturbances, medication intake for sleep, and daytime sleepiness. A total score of 5 or higher indicates low sleep quality (Buysse et al., 1989). Satisfactory reliability (Cronbach's α = 0.65) has been shown for the arabic version of the PSQI (Suleiman et al., 2010)
Physical Assessments
Resting Electrocardiogram
The 12-lead resting Electrocardiogram (ECG) is part of the medical diagnostics and performed to screen for cardiac disease. It is performed at T0, T1 and T2. During the resting ECG participants are asked to lay down quietly for 5 minutes in ambient conditions. Resting heart rate is derived from ECG recordings.
Spiroergometry
Spiroergometry is used to determine the eligibility for participation and performed at T0, T1 and T2 to further assess the training effect during MAET. Spiroergometry is carried out on the bicycle (Lode Excalibur Sport, Lode Medical Technology, Groningen, Netherlands) using a step-wise protocol to determine maximum aerobic capacity. Individual seat and handlebar position is maintained throughout. Depending on age, gender, and body weight, participants started cycling at 25 W or 50 W and workload was increased every 3 min by 25 W or 50 W until exhaustion. Gas exchange parameters are measured continuously with a MetaMax II metabolic test system (Cortex Biophysik, Leipzig, Germany; mixing chamber; sampling frequency 10 s). Time courses of oxygen consumption (VO2) and respiratory minute ventilation (VE) were calculated using the mean of 3 contiguous values at exhaustion for the determination of maximal oxygen consumption. Based on an untrained sample of refugees, exercising to maximum exhaustion cannot always be assumed. Thus, in addition blood lactate concentrations are measured for the determination of lactate thresholds, which represent submaximal aerobic performance parameters that are independent of maximal exhaustion. Arterialized capillary blood is obtained from the hyperemised earlobe for analyzing blood lactate (BLa; enzymatic-amperometric method, Greiner, Flacht, Germany) at rest, at the end of each step, at cessation and 1, 3, and 5 min post-exercise. Blood pressure is measured manually at rest, at the end of each step, and 1, 3, 5 min post-exercise.
Stress Electrocardiogram
The 12-lead stress ECG is recorded during spiroergometry at T0, T1 and T2. Maximum heart rate is derived from ECG recordings. Based on the resting heart rate and the maximal heart rate during incremental exercise to voluntary exhaustion, the individual heart rate zones for MAET (60% heart rate reserve (+/- 5 bpm)) are determined.
Blood Parameters
A Complete Blood Count (CBC) by obtaining venous blood samples from the antecubital vein (following the general medical examination and prior to spiroergometry at T0) gives an overview of possible impairments that may lead to exclusion (see Participants and eligibility criteria)
Additional Measures
Socio-demographic Information
Participants’ age, sex, region of origin, native speech, further languages, medication, family status and duration of living in Germany are assessed once prior to study inclusion.
Comorbidities
The Structured Clinical Interview for DSM-5 Clinician Version (SCID-5-CV; First et al., 2016) is conducted to assess further comorbid psychological disorders in a semi-structured interview at T0. The SCID-5-CV's reliability varies depending on study design, rate of disorders and study sample. A reliability of at least .70 can be assumed (First et al., 2016). Symptoms of PTSD and depression, which are already explored by CAPS, WAEC and HAM-D, are not assessed with the SCID-5-CV.
Motivation in Moderate-intensity Aerobic Exercise Training
Participants are interviewed concerning their motivation during MAET at T1. Questions on motivational factors are answered for supervised group training and unsupervised training separately. Participants are asked to indicate their motivation for MAET post hoc for the start of the training and at present (after the end of the training) on a five-point scale ranging from 1 = 'Very unmotivated' to 5 = 'Very motivated'. The change in motivation during the MAET is also recorded on a five-point scale, the extremes of which range from 1 = 'Motivation has decreased a lot' to 5 = 'Motivation has increased a lot'. In addition, further motivational aspects of the MAET are assessed with 9 items, such as 'The expected effect of exercise on physical health'; 'Social contact'; 'Exercise outdoors/ in nature' regarding their motivating character for MAET on a five-point Likert scale from 1 = 'very motivating' to 5 = 'not at all motivating'.
Data Management
Statistical Methods
All statistical analyses will be conducted by a member of the research team, who was not involved in the data collection process and the study interventions, using R version 4.1.2 (R Core Team, 2021). Alpha level for the main analyses is set to .025 due to multiple primary outcomes. The main hypotheses will be tested with multiple 2x3 mixed ANOVA’s (group: NET+ vs. NET; time: pre vs. post vs. six-month follow-up) to examine symptom severity in primary outcomes (PTSD and depression). The same statistical analyses will be performed for the secondary outcomes (general mental health problems, sleep quality and agoraphobia). Contrasts will be conducted to separately examine the group-specific development of symptom severity over time (T0 vs T1; T0 vs T2; T1 vs T2). In addition, moderator analyses and mediator analyses examining the impact of secondary outcomes and demographic data in the effect of MAET in primary outcomes, will be conducted.
Dealing with missing data
The statistical analyses will include the whole sample data of the RCT. Participants that meet the inclusion criteria will be included in the trial and considered in the analyses. Dropping out of trial will not exclude participants from final analyses. In this case the missing data will be imputed using Fully Conditional Specification (FCS; Sterne et al., 2009).