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

Stress Disorders, Post-Traumatic Clinical Trial

— MOSES  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03894774
• Other study ID #: MOSES
• Status: Completed
• Phase: N/A
• Start date: December 5, 2012
• Est. completion date: August 31, 2019

Study information

• Verified date: February 2020
• Source: Klinikum der Universitaet Muenchen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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;

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: August 31, 2019
• Est. primary completion date: October 17, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 13 Years

Eligibility

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

Related Conditions & MeSH terms

• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Behavioral:
• Intensive in-patient psychotherapy treatment
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.

Other:
• Treatment as usual
Combination of behavioral or psychoanalytic outpatient psychotherapy and pharmacotherapy

Locations

Country	Name	City	State
Germany	Department of Pediatrics, Dr. von Hauner Children`s Hospital, University Hospital, LMU Munich	Munich

Sponsors (2)

Lead Sponsor	Collaborator
Klinikum der Universitaet Muenchen	Max-Planck-Institute of Psychiatry

Country where clinical trial is conducted

Germany, 

References & Publications (7)

D'Andrea W, Ford J, Stolbach B, Spinazzola J, van der Kolk BA. Understanding interpersonal trauma in children: why we need a developmentally appropriate trauma diagnosis. Am J Orthopsychiatry. 2012 Apr;82(2):187-200. doi: 10.1111/j.1939-0025.2012.01154.x. Review. — View Citation

Gillies D, Taylor F, Gray C, O'Brien L, D'Abrew N. Psychological therapies for the treatment of post-traumatic stress disorder in children and adolescents (Review). Evid Based Child Health. 2013 May;8(3):1004-116. doi: 10.1002/ebch.1916. Review. — View Citation

Gold AL, Sheridan MA, Peverill M, Busso DS, Lambert HK, Alves S, Pine DS, McLaughlin KA. Childhood abuse and reduced cortical thickness in brain regions involved in emotional processing. J Child Psychol Psychiatry. 2016 Oct;57(10):1154-64. doi: 10.1111/jcpp.12630. — View Citation

Hamilton, L., Micol-Foster, V., & Muzik, M. Childhood maltreatment trauma: Relevance for adult physical and emotional health. A Review. Trauma Cases and Reviews, 1(003), 2015.

Heim C, Binder EB. Current research trends in early life stress and depression: review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Exp Neurol. 2012 Jan;233(1):102-11. doi: 10.1016/j.expneurol.2011.10.032. Epub 2011 Nov 7. Review. — View Citation

Pechtel P, Pizzagalli DA. Effects of early life stress on cognitive and affective function: an integrated review of human literature. Psychopharmacology (Berl). 2011 Mar;214(1):55-70. doi: 10.1007/s00213-010-2009-2. Epub 2010 Sep 24. Review. — View Citation

Teicher MH, Samson JA, Anderson CM, Ohashi K. The effects of childhood maltreatment on brain structure, function and connectivity. Nat Rev Neurosci. 2016 Sep 19;17(10):652-66. doi: 10.1038/nrn.2016.111. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Behavioral Symptoms 1: Child Behaviour Checklist (CBCL)	Total Problems Score: 0-28="normal", 29-37="borderline", 38-236="clinical"	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)
Other	Behavioral Symptoms 2: Child Behaviour Checklist (CBCL)	Externalizing Behaviour: 0-12="normal", 13-16="borderline", 17-66="clinical";	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)
Other	Behavioral Symptoms 3: Child Behaviour Checklist (CBCL)	Internalizing Behaviour: 0-7="normal", 8-9="borderline", 10-62="clinical";	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)
Other	Behavioral Symptoms 4: Strength and Difficulties Questionnaire (SDQ).	Total difficulties score: 0-13="normal", 14-16="borderline", 17-40="abnormal";	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)
Other	Behavioral Symptoms 5: Strength and Difficulties Questionnaire (SDQ).	hyperactivity score: 0-5="normal", 6="borderline", 7-10="abnormal"	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)
Other	Posttraumatic Symptoms	Parent Repot of Posttraumatic Symptoms (PROPS). If total testscore is greater than 16 a posttraumatic stress disorder is suspected. Total Score range: 0-60.	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)
Other	Dissociation Symptoms	Child Dissociation Scale (CDC). If total testscore is greater than 11 a dissociative disorder is suspected. Total Score range: 0-18.	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)
Other	Depression Symptoms	Depression Inventory for Children and Young People (DIKJ - Depressionsinventar für Kinder und Jugendliche) If the testscore is greater than 14 a depression is suspected. Testscore range: 0-58.	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)
Other	Anxiety Symptoms	Anxiety Questionnaire (FAS - Fragebogen für Angststörungen). If total testscore is greater than 24 a anxiety disorder is suspected. Total testscore range 0-82.	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)
Other	Cognitive Functioning	Working Memory form Wechsler Intelligence Scale for Children (WISC-IV).; At t0/t1 a full-scale intelligence test was conducted (IQ). To minimize learning effects through rehearsal, we focused on subtests in the follow-up testing: Digit Span (forward, backward); Letter-Number Sequencing; By combining both subtest scores we calculate the Working Memory Index Score. The Working Memory Index will be used to address changes in cognitive functioning.	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)
Other	Attachment Representations	Child Attachment Interview (CAI). Changes in attachment representations in a qualitative binary secure-insecure distinction and in a four category qualitative coding classification (secure, dismissing, preoccupied, disorganized).	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)