Clinical trial NCT05149352: RESET-psychotherapy: the Effectiveness of Trauma-focused Therapy in Patients With Depression and Childhood Trauma
Official title: REStoring Mood After Early Life Trauma: the Effectiveness of Trauma-focused Therapy in Patients With Depression and Childhood Trauma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Major Depressive Disorder
Childhood Trauma
Keywords: Depression
Childhood trauma
Trauma-focused
Psychotherapy
Treatment
EMDR
Imagery rescripting
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Stichting tot steun VCVGZ
name: HSK Groep B.V.
name: Altrecht
First posted: 2021-12-08
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to one of two treatment conditions. In one condition (control group) participants will receive a regular depression treatment that they would usually receive for their depression ('treatment as usual', TAU). In the other condition (intervention group) participants will receive trauma-focused therapy (TFT), additional and parallel to their depression treatment (TAU). In both treatment groups (TAU and TAU+TFT), treatment will be provided during a period of 12 weeks.
Primary purpose: TREATMENT

Brief summary: Depression is a debilitating psychiatric disorder with a recurrent and progressive course. Around 25% of depressive patients has experienced moderate to severe levels of childhood trauma (CT), resulting in earlier onset and more severe and recurrent depressions. There is currently no targeted treatment for CT-related depression. This is problematic as patients with CT-related depression respond poorly to standard depression treatments. The RESET-psychotherapy study proposes an innovative, targeted disease-modifying treatment strategy for CT-related depression. The main objective is to investigate the effectiveness of trauma-focused therapy (TFT), as an addition to regular depression treatment ('treatment as usual'; TAU), in reducing depression symptom severity in patients with CT-related depression. 158 adult patients will be randomized to receive a 12-week treatment with 1) TAU or 2) TFT in combination with TAU. The primary outcome measure is defined as depression symptom severity after 12 weeks treatment (post-treatment), measured with the Inventory of Depressive Symptomatology - Self Rated (IDS-SR).

Detailed description: Depression is a debilitating psychiatric disorder with a recurrent and progressive course. Even though antidepressants and psychotherapy are often effective, a substantial proportion of patients does not respond to currently used evidence-based treatments. Around 25% of depressive patients has experienced moderate to severe levels of childhood trauma (CT), ranging from physical and emotional neglect to emotional, physical and sexual abuse. There is increasing evidence that depression related to childhood trauma (CT) is critically different from non-CT related depression: it emerges earlier in life with more severe and recurrent symptoms and has worse treatment outcomes. Therefore, there is a large and unmet need for novel therapeutic strategies for CT-related depression. Currently, there is no targeted treatment available for CT-related depression. Given the major role of trauma in CT-related depression, it is plausible that trauma-focused psychotherapies may be effective in this depression subtype. The current study aims to investigate the effectiveness of trauma-focused therapy (TFT), as an addition to 'treatment as usual' (TAU), in reducing depression symptom severity in patients with CT-related depression. It is expected that trauma-focused therapy will be a safe and rational strategy to enhance resilience and improve depression outcomes for patients with CT-related depression. RESET-psychotherapy is a 12-week randomized controlled clinical trial (single-blind RCT), in which TFT in combination with TAU will be compared to TAU only at various specialized mental healthcare units of mental health care institutions. The study population will consist of 158 adult patients who have a diagnosis of moderate to severe depression (according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)) and moderate to severe childhood trauma (CT). The primary outcome measure is defined as depression symptom severity after 12 weeks treatment (post-treatment), measured with the Inventory of Depressive Symptomatology - Self Rated (IDS-SR). Data will be collected during multiple assessments: at baseline (T0), after 6 weeks (T1), after 12 weeks (T2; post-treatment), and after 6 months post-treatment (follow-up, T3). Information about depressive symptoms, childhood trauma and other health-related outcomes will be assessed using self-report questionnaires and semi-structured clinical interviews. In addition, to better understand how and for who TFT works, stress-related biomarkers (hair cortisol, inflammatory and epigenetic biomarkers in the blood) will be examined pre- and post-treatment. A sub-group of patients (N=60, 30 per intervention group) will be asked to undergo fMRI scans pre- and post-treatment to measure stress-related brain activity (fMRI sub-study, ±60 minutes per fMRI session).

Eligibility criteria: Inclusion Criteria:

* Moderate to severe depression, defined by a score ≥ 26 on the Inventory of Depressive Symptomatology - Self Rated (IDS-SR)
* DSM-5 diagnosis of MDD confirmed with the Dutch translation of the MINI-S for DSM-5
* Moderate to severe childhood trauma (CT) before the age of 18, defined by a score above validated cut-off on one or more of the following domains of the 28-item Childhood Trauma Questionnaire Short Form (CTQ-SF):

  * physical neglect: score ≥ 10
  * emotional neglect: score ≥ 15
  * sexual abuse: score ≥ 8
  * physical abuse: score ≥10
  * emotional abuse: score ≥ 13
* Sufficient mastery of Dutch language

Exclusion Criteria:

* Previous TFT on CT
* Other lifetime severe psychiatric comorbidity (bipolar disorder, psychotic disorder)
* Current alcohol/drug dependence
* Primary diagnosis of post-traumatic stress disorder (PTSD) or Acute Stress Disorder (ASD)
* Lifetime diagnosis of borderline personality disorder (BPD)

Primary outcomes:
measure: Depressive symptom severity at post-treatment
timeFrame: Up to 12 weeks (post-treatment)
Secondary outcomes:
measure: Depressive symptom severity during treatment and at 9 months follow-up
timeFrame: Up to 9 months (follow-up)
measure: Remission in CT-related depression
timeFrame: Up to 9 monts (follow-up)
Other outcomes:
measure: Functional disability
timeFrame: Up to 9 months (follow-up)
measure: Anxiety symptoms
timeFrame: Up to 9 months (follow-up)
measure: Insomnia
timeFrame: Up to 9 months (follow-up)
measure: Subjective stress
timeFrame: Up to 9 months (follow-up)
measure: Suicidality
timeFrame: Up to 9 months (follow-up; if participants report suicidal ideation when completing the IDS-SR or undergoing the M.I.N.I. interview)
measure: Hair cortisol (stress-related biomarker)
timeFrame: Up to 12 weeks (post-treatment)
measure: Inflammatory markers (stress-related biomarkers)
timeFrame: Up to 12 weeks (post-treatment)
measure: Epigenetic markers (stress-related biomarkers)
timeFrame: Up to 12 weeks (post-treatment)
measure: Brain structure - T1 (fMRI sub-study, not yet started, anticipated start April 2022)
timeFrame: Up to 12 weeks (post-treatment)
measure: Brain structure - DTI (fMRI sub-study, not yet started, anticipated start April 2022)
timeFrame: Up to 12 weeks (post-treatment)
measure: Functional dynamics of spontaneous neural activity (fMRI sub-study, not yet started, anticipated start April 2022)
timeFrame: Up to 12 weeks (post-treatment)
measure: Working memory (fMRI sub-study, not yet started, anticipated start April 2022)
timeFrame: Up to 12 weeks (post-treatment)
measure: Emotion regulation (fMRI sub-study, not yet started, anticipated start April 2022)
timeFrame: Up to 12 weeks (post-treatment)
measure: Reward Processing (fMRI sub-study, not yet started, anticipated start April 2022)
timeFrame: Up to 12 weeks (post-treatment)
Locations:
city: Amsterdam
country: Netherlands
facility: GGZ inGeest
state: Noord-Holland
city: Woerden
country: Netherlands
facility: HSK Groep
state: Utrecht
city: Utrecht
country: Netherlands
facility: Altrecht
Study officials:
affiliation: Amsterdam UMC, location VUmc and GGZ inGeest
name: Christiaan H Vinkers, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.
citation: McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication II: associations with persistence of DSM-IV disorders. Arch Gen Psychiatry. 2010 Feb;67(2):124-32. doi: 10.1001/archgenpsychiatry.2009.187.
citation: Teicher MH, Samson JA. Childhood maltreatment and psychopathology: A case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. Am J Psychiatry. 2013 Oct;170(10):1114-33. doi: 10.1176/appi.ajp.2013.12070957.
citation: Nanni V, Uher R, Danese A. Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry. 2012 Feb;169(2):141-51. doi: 10.1176/appi.ajp.2011.11020335.
citation: Spijker J, Bockting C, Meeuwissen J, Van Vliet I, Emmelkamp P, Hermens M, et al. Multidisciplinaire richtlijn Depressie (Derde revisie): Richtlijn voor de diagnostiek, behandeling en begeleiding van volwassen patiënten met een depressieve stoornis. Trimbos Instituut: Utrecht. 2013
citation: Driessen A., ten Broeke E. Schematherapie en EMDR gecombineerd bij complexe traumagerelateerde problematiek. Tijdschrift voor Gedragstherapie; 2014.