Evaluation of an Intensive Inpatient Psychotherapy Treatment for Severely and Early Traumatized Children (MOSES)

Study Overview
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Brief Summary
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Evaluation of longitudinal treatment effects applying an intensive psychotherapeutic intervention for inpatients (age of participants: 6-13 years) with a multi-method-approach to address the complex nature of severe childhood trauma. (Chronic Post-Traumatic Stress Disorder)

Detailed Description
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Severe adversity and trauma in early childhood have been associated with a highly increased risk for a variety of psychiatric disorders, lasting into adulthood. This increased risk is accompanied by a set of biological changes ranging from changes in cortical thickness to endocrinological changes. At a behavioral level, children with complex PTSD (developmental trauma disorder) show severe and long-lasting negative effects. Such children exhibit a wide range of symptoms: affect dysregulation, attention difficulties, impairment in interpersonal relationships, aggressive and dissociative behaviour, disturbances of cognition. Corresponding alterations in neural networking and brain development are well studied. Although evidence-based treatment approaches for children with non-complex PTSD exist, complex-traumatized children have no well-evaluated treatments. Furthermore, early intervention can prevent the chronification and exacerbation of symptoms and promote social adaptation and participation.The following topics will be addressed: (1) brain development (Multimodal MRI (mMRI) including anatomical (T1-MPRAGE, T2-FLAIR, DTI-Diffusion Tensor Imaging) and functional MRI measurements (resting-state functional MRI, task fMRI (presenting affective pictures according to the International Affective Picture System, IAPS), EEG); (2) alterations in neuroendocrinological systems involved in stress regulation (Cortisol, Oxytocin, Vasopressin); (3) behavioral symptoms; (4) cognitive functioning; (5) attachment representations of children and their primary caregivers;

Official Title
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Evaluation of an Intensive Inpatient Psychotherapy Treatment for Severely and Early Traumatized Children - Clinical Pilot Study Including Multimodal Mri (MOSES)

Conditions
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Stress Disorders, Post-Traumatic

Intervention / Treatment
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* Behavioral: Intensive in-patient psychotherapy treatment
* Other: Treatment as usual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe early traumatization with experiences of violence, neglect, abuse and chronic symptoms related to complex PTSD. Exclusion Criteria: Autism spectrum disorder Addiction disorder Mental disability (IQ < 85) Endangerment to themselves or others

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: The study was conducted in the following randomized waiting control design: After being included in the study at time T0 the children stay in Treatment-As-Usual (TAU) for at least three months and are then randomly assigned to the Intensive Inpatient Psychotherapy Treatment Group (IG) or the Waiting Control Group (WCG) after this TAU time period (This period is considered necessary and sufficient in order to reliably estimate possible trends of changes in the brain). The children in the WCG stay in TAU and are assigned to the IG as soon as a treatment place is available. The waiting period will be included in the analysis as a confounder. The third group is a Healthy Control Group (HCG) of matched pairs (matched for gender, age and handedness).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive InPatient Psychotherapy Treatment Group (IG)<br>Intensive non-pharmaceutical inpatient intervention with high degrees of individual psychotherapy (5 sessions a week, psychodynamic and specific trauma therapy), group therapy (music-, arts-, sports- and concentrative movement therapy - each one session a week) as well as an ongoing milieutherapeutic frame where patients live over the whole treatment (approximately a 1:1-ratio caregiver per patient is given) of 6 to 8 month treatment duration. | Behavioral: Intensive in-patient psychotherapy treatment<br>* Intensive non-pharmaceutical in-patient intervention with high degrees of individual psychotherapy (5 sessions a week, psychodynamic and specific trauma therapy), group therapy (music-, arts-, sports- and concentrative movement therapy - each one session a week) as well as an ongoing milieutherapeutic setting where patients live during the whole treatment (approximately a 1:1-Ratio caregiver per patient is given) of 6 to 8 month treatment duration.<br>|
| Active Comparator: Waiting Control Group (WCG)<br>Treatment as usual (mostly combination of behavioral or psychoanalytic outpatient psychotherapy and pharmacotherapy). Duration: At least 3 month to a maximum of 6 month. | Other: Treatment as usual<br>* Combination of behavioral or psychoanalytic outpatient psychotherapy and pharmacotherapy<br>|
| No Intervention: Healthy Control Group (HCG)<br>Matched Pairs design to control for gender, age and handedness. HCG measurements are planned and conducted according to the exact durations of their matched inpatient pair of the IG. Mandatory to control for effects of factors such as brain maturation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Structural MRI (T1w, T2w, DTI) | All structural images will be acquired in a 3 Tesla MR system using a 20- channel head-coil (Siemens, Erlangen). Data post-processing will be performed with lab-internal scripts developed for a multi-core cluster. For structural analyses of T1w, T2w and DTI data, freesurfer,FSL and workbench will be used. T1w and T2w data will be volumetrically analyzed and the results will be reported in mm3. DTI data will be processed using tbss-FSL and probtrackX-FSL. DTI will be quantified in regard of the number of white matter fiber bundles within regions-of-interest (ROIs) and from-ROI-to-ROI. The Dosenbach atlas (Dosenbach et al. 2010) and the multimodal Brainetome atlas (Fan et al. 2016) will be used for all structural analyses. It is an explorative study that follows a whole-brain approach. Changes in emotion-processing and trauma-associated brain regions such as the hippocampus,the amygdala,the orbitofrontal cortex and the insula are assumed | longitudinal (4 measurements, t0: at least 3 month before treatment, t1: at admission to treatment, t2: at discharge (average of 8 month), t3: 6 month post treatment) | 
| Resting state functional MRI connectivity (rsfcMRI) | EPI-sequence: fMRI will be carried out at 3 Tesla (Siemens) scanner using a 20- channel head-coil. For functional imaging, an EPI sequence with the following parameters will be used: repetition time (TR),2000 ms; echo time (TE),30 ms; flip angle (FA), 80°; spatial resolution, 3 × 3 × 3 mm3; imaging matrix, 64 × 64; field-of-view (FoV), 192 × 192 mm2; number of slices: 36; number of volumes: 200. Data post-processing will be performed with lab-internal scripts developed for a multicore cluster. For rsfcMRI analyses of freesurfer,FSL,AFNI and workbench will be used. rsfcMRI will be quantified as number of significant activated voxels (spatial extent) and connectivity strength (z-scores).Networks of interest (ICA-based): Salience network, Default Mode Network. Regions of interest (seed-based): hippocampus, the amygdala, the orbitofrontal cortex and the insula.In addition, a RS-EEG with 19 scalp electrodes is used to complement rsfcMRI,which is cortically evaluated using Brainstorm. | longitudinal (4 measurements, t0: at least 3 month before treatment, t1: at admission to treatment, t2: at discharge (average of 8 month), t3: 6 month post treatment) | 
| Task-based fMRI using the International affective picture system (IAPS) | For the task-based fMRI the same EPI sequence will be used as for the resting state (see outcome 2). The number of volumes: 180. Three different sets of each 45 (15 neutral, 15 negative, 15 positive rated pictures) pictures were created and randomly displayed during the scanning procedure and also afterward to control for personal affective valence and arousal with Self-Assessment Manikin (SAM). Data post-processing will be performed with FSL-FEAT using a block-design. Regions of interest follow the previous structural and rsfcMRI analyses ROIs: hippocampus, amygdala, orbitofrontal cortex and the insula. | longitudinal (4 measurements, t0: at least 3 month before treatment, t1: at admission to treatment, t2: at discharge (average of 8 month), t3: 6 month post treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alterations in neuroendocrinological systems involved in stress regulation | Oxytocin (pg/ml in Saliva) release of active stress regulation throughout relaxation using attachment interviews as stressors. Oxytocin will be analysed using radioimmunoassays in an external lab (Landgraf Riagnosis, MPI). | longitudinal (4 measurements, t0: at least 3 month before treatment, t1: at admission to treatment, t2: at discharge (average of 8 month), t3: 6 month post treatment) | 
| Alterations in neuroendocrinological systems involved in stress regulation 2 | Cortisol (ng/mL in Saliva) release in active stress regulation throughout relaxation using attachment interviews as stressors. Cortisol will be analysed by Endocrine Laboratories, Department of Medicine IV, University Hospital, LMU Munich. | longitudinal (4 measurements, t0: at least 3 month before treatment, t1: at admission to treatment, t2: at discharge (average of 8 month), t3: 6 month post treatment) | 
| Alterations in neuroendocrinological systems involved in stress regulation 3 | Vasopressin (pg/ml in Saliva) release of active stress regulation throughout relaxation using attachment interviews as stressors. Vasopressin will be analysed using radioimmunoassays in an external lab (Landgraf Riagnosis, MPI). | longitudinal (4 measurements, t0: at least 3 month before treatment, t1: at admission to treatment, t2: at discharge (average of 8 month), t3: 6 month post treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Post-Traumatic Stress Disorder, Neuroses, Posttraumatic, PTSD