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RESET-psychotherapy: the Effectiveness of Trauma-focused Therapy in Patients With Depression and Childhood Trauma

Primary Purpose

Major Depressive Disorder, Childhood Trauma

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Treatment as usual (TAU) for depression
Trauma-focused therapy (TFT)
Sponsored by
Amsterdam UMC, location VUmc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Depression, Childhood trauma, Trauma-focused, Psychotherapy, Treatment, EMDR, Imagery rescripting

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • GGZ inGeestRecruiting
  • HSK GroepRecruiting
  • Altrecht

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Treatment as usual (TAU)

Treatment as usual (TAU) + Trauma-focused therapy (TFT)

Arm Description

Participants will receive an evidence-based psychotherapeutic intervention combined with/or pharmacotherapy (TAU)

Participants will receive 6 to 10, 60-90 minute TFT sessions delivered over a period of 12 weeks, in addition to TAU.

Outcomes

Primary Outcome Measures

Depressive symptom severity at post-treatment
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)

Secondary Outcome Measures

Depressive symptom severity during treatment and at 9 months follow-up
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)
Remission in CT-related depression
The presence or absence of DSM-5 Major Depressive Disorder (MDD), identified using the Major Depressive Disorder (MDD) section of the Dutch translation of the Mini International Neuropsychiatric Interview-Simplified (MINI-S).

Full Information

First Posted
November 2, 2021
Last Updated
April 20, 2022
Sponsor
Amsterdam UMC, location VUmc
Collaborators
Stichting tot steun VCVGZ, HSK Groep B.V., Altrecht
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1. Study Identification

Unique Protocol Identification Number
NCT05149352
Brief Title
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

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 10, 2021 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
Collaborators
Stichting tot steun VCVGZ, HSK Groep B.V., Altrecht

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Childhood Trauma
Keywords
Depression, Childhood trauma, Trauma-focused, Psychotherapy, Treatment, EMDR, Imagery rescripting

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
Outcomes Assessor
Masking Description
As the interventions in these studies are psychotherapies, both participants and care providers cannot be masked from the treatment allocation. To ensure the objectivity of the research measures, the outcome assessors will be blinded to the allocated treatment condition.
Allocation
Randomized
Enrollment
158 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment as usual (TAU)
Arm Type
Active Comparator
Arm Description
Participants will receive an evidence-based psychotherapeutic intervention combined with/or pharmacotherapy (TAU)
Arm Title
Treatment as usual (TAU) + Trauma-focused therapy (TFT)
Arm Type
Experimental
Arm Description
Participants will receive 6 to 10, 60-90 minute TFT sessions delivered over a period of 12 weeks, in addition to TAU.
Intervention Type
Behavioral
Intervention Name(s)
Treatment as usual (TAU) for depression
Intervention Description
TAU for depression will be largely determined by the Dutch multidisciplinary practice guideline on depression (Spijker et al., 2013). This means that patients with CT-related depression will receive good clinical care, e.g. evidence-based psychotherapeutic interventions, such as cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) combined with/or pharmacotherapy. Therapists who give TAU are not allowed to provide a trauma-focused intervention aimed at CT during the 12-week intervention period.
Intervention Type
Behavioral
Intervention Name(s)
Trauma-focused therapy (TFT)
Intervention Description
The content of TFT, delivered by another therapist than the therapist that will provide TAU, depends on the type of CT the patient reports. If the patient predominantly reports experiences of abuse, there are often clear memories of this abuse ('target images') present and Eye Movement Desensitization and Reprocessing (EMDR) is recommended as the treatment strategy. If the patient predominantly reports experiences of neglect, memories are often less identifiable, although these experiences can have a big impact on the development of maladaptive schemas. In this case, imagery rescripting (ImRs) is recommended as treatment strategy. If the patient reports both experiences of abuse and neglect, the therapist will discuss with the patient which type of CT has the greatest impact on the current depressive symptoms and starts with the indicated therapy. If indicated, the therapist can switch between EMDR and ImRs after a minimum of 4 sessions.
Primary Outcome Measure Information:
Title
Depressive symptom severity at post-treatment
Description
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)
Time Frame
Up to 12 weeks (post-treatment)
Secondary Outcome Measure Information:
Title
Depressive symptom severity during treatment and at 9 months follow-up
Description
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)
Time Frame
Up to 9 months (follow-up)
Title
Remission in CT-related depression
Description
The presence or absence of DSM-5 Major Depressive Disorder (MDD), identified using the Major Depressive Disorder (MDD) section of the Dutch translation of the Mini International Neuropsychiatric Interview-Simplified (MINI-S).
Time Frame
Up to 9 monts (follow-up)
Other Pre-specified Outcome Measures:
Title
Functional disability
Description
General functioning and disability in major life domains, measured with the 12-item WHO Disability Schedule (WHODAS; with a total score ranging from 12 to 60, where higher scores indicate more disability or loss of function).
Time Frame
Up to 9 months (follow-up)
Title
Anxiety symptoms
Description
The presence and severity of anxiety symptoms, determined with the Beck Anxiety Inventory (BAI; with a total score ranging from 0 to 63, where higher scores indicate higher severity of anxiety symptoms)
Time Frame
Up to 9 months (follow-up)
Title
Insomnia
Description
Insomnia severity, measured with with the Insomnia Severity Index (ISI; with a total score ranging from 0-28, where higher scores indicate higher insomnia severity).
Time Frame
Up to 9 months (follow-up)
Title
Subjective stress
Description
Subjective stress, determined with the Perceived Stress Scale (PSS; with a total score ranging from 0-40, where higher scores reflect greater perceived stress)
Time Frame
Up to 9 months (follow-up)
Title
Suicidality
Description
The presence of suicidal ideation or behavior, determined with a shortened version of the Columbia-Suicide Severity Rating Scale (C-SSRS). The suicidal ideation scale ranges from 0-5, where a score of 4 reflects an active suicidal ideation with some intent to act, but without a specific plan and a score of 5 reflects an active suicidal ideation with a specific plan and intent.
Time Frame
Up to 9 months (follow-up; if participants report suicidal ideation when completing the IDS-SR or undergoing the M.I.N.I. interview)
Title
Hair cortisol (stress-related biomarker)
Description
Long-term cortisol levels, assessed by hair samples collected pre - and post-treatment
Time Frame
Up to 12 weeks (post-treatment)
Title
Inflammatory markers (stress-related biomarkers)
Description
Levels of C-reactive protein (CRP), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6), assessed by blood samples drawn pre - and post-treatment
Time Frame
Up to 12 weeks (post-treatment)
Title
Epigenetic markers (stress-related biomarkers)
Description
The DNA, extracted from blood samples drawn pre - and post-treatment, will be used for future exploratory epigenetic research. Epigenetic changes will be analyzed genome-wide using microarrays.
Time Frame
Up to 12 weeks (post-treatment)
Title
Brain structure - T1 (fMRI sub-study, not yet started, anticipated start April 2022)
Description
A T1-weighted structural image will be acquired in order to obtain a high-resolution anatomic image of the brain with contrast between grey matter, white matter and CSF (cerebral spinal fluid).
Time Frame
Up to 12 weeks (post-treatment)
Title
Brain structure - DTI (fMRI sub-study, not yet started, anticipated start April 2022)
Description
White matter (WM) tract integrity will be investigated by acquiring diffusion tensor images.
Time Frame
Up to 12 weeks (post-treatment)
Title
Functional dynamics of spontaneous neural activity (fMRI sub-study, not yet started, anticipated start April 2022)
Description
Resting state fMRI (T2*-weighted echo planar images (EPIs), sensitive to blood oxygenation level-dependent (BOLD) contrast, will be obtained, covering the entire brain under rest)
Time Frame
Up to 12 weeks (post-treatment)
Title
Working memory (fMRI sub-study, not yet started, anticipated start April 2022)
Description
Task-based fMRI** (T2*-weighted echo planar images (EPIs), sensitive to blood oxygenation level-dependent (BOLD) contrast, will be obtained, covering the entire brain under rest) ** Precise task to be determined; probably the n-back task or the digit-span task.
Time Frame
Up to 12 weeks (post-treatment)
Title
Emotion regulation (fMRI sub-study, not yet started, anticipated start April 2022)
Description
Task-based fMRI (situation-focused volitional reappraisal task; T2*-weighted echo planar images (EPIs), sensitive to blood oxygenation level-dependent (BOLD) contrast, will be obtained, covering the entire brain)
Time Frame
Up to 12 weeks (post-treatment)
Title
Reward Processing (fMRI sub-study, not yet started, anticipated start April 2022)
Description
Task-based fMRI (social incentive delay task; T2*-weighted echo planar images (EPIs), sensitive to blood oxygenation level-dependent (BOLD) contrast, will be obtained, covering the entire brain)
Time Frame
Up to 12 weeks (post-treatment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anouk W Gathier, Drs.
Phone
0031207884675
Email
a.gathier@ggzingeest.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christiaan H Vinkers, Prof. dr.
Organizational Affiliation
Amsterdam UMC, location VUmc and GGZ inGeest
Official's Role
Principal Investigator
Facility Information:
Facility Name
GGZ inGeest
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1081HJ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anouk W Gathier, Drs.
Phone
0031207884675
Email
a.gathier@ggzingeest.nl
Facility Name
HSK Groep
City
Woerden
State/Province
Utrecht
ZIP/Postal Code
3447GN
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maarten JM Merkx, Dr.
Phone
0031263687701
Email
m.merkx@hsk.nl
Facility Name
Altrecht
City
Utrecht
ZIP/Postal Code
3524SH
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pieter Dingemanse, Drs.
Phone
031302308790
Email
p.dingemanse@altrecht.nl

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices)
IPD Sharing Time Frame
Immediately following publication, no end date.
IPD Sharing Access Criteria
Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.
Citations:
PubMed Identifier
17074942
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.
Results Reference
background
PubMed Identifier
20124112
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.
Results Reference
background
PubMed Identifier
23982148
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.
Results Reference
background
PubMed Identifier
22420036
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. Erratum In: Am J Psychiatry. 2012 Apr;169(4):439.
Results Reference
background
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
Results Reference
background
Citation
Driessen A., ten Broeke E. Schematherapie en EMDR gecombineerd bij complexe traumagerelateerde problematiek. Tijdschrift voor Gedragstherapie; 2014.
Results Reference
background

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RESET-psychotherapy: the Effectiveness of Trauma-focused Therapy in Patients With Depression and Childhood Trauma

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