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

Major Depressive Disorder Clinical Trial

Official title:

REStoring Mood After Early Life Trauma: the Effectiveness of Trauma-focused Therapy in Patients With Depression and Childhood Trauma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05149352
• Other study ID #: NL74405.029.20
• Status: Recruiting
• Phase: N/A
• Start date: November 10, 2021
• Est. completion date: March 1, 2024

Study information

• Verified date: April 2022
• Source: Amsterdam UMC, location VUmc
• Contact: Anouk W Gathier, Drs.
• Phone: 0031207884675
• Email: a.gathier[@]ggzingeest.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 158
• Est. completion date: March 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Childhood Trauma
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Wounds and Injuries

Intervention

Behavioral:
• Treatment as usual (TAU) for depression
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.
• Trauma-focused therapy (TFT)
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.

Locations

Country	Name	City	State
Netherlands	GGZ inGeest	Amsterdam	Noord-Holland
Netherlands	Altrecht	Utrecht
Netherlands	HSK Groep	Woerden	Utrecht

Sponsors (4)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc	Altrecht, HSK Groep B.V., Stichting tot steun VCVGZ

Country where clinical trial is conducted

Netherlands, 

References & Publications (6)

Driessen A., ten Broeke E. Schematherapie en EMDR gecombineerd bij complexe traumagerelateerde problematiek. Tijdschrift voor Gedragstherapie; 2014.

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. — View 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. Erratum in: Am J Psychiatry. 2012 Apr;169(4):439. — View 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. — View 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

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Functional disability	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).	Up to 9 months (follow-up)
Other	Anxiety symptoms	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)	Up to 9 months (follow-up)
Other	Insomnia	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).	Up to 9 months (follow-up)
Other	Subjective stress	Subjective stress, determined with the Perceived Stress Scale (PSS; with a total score ranging from 0-40, where higher scores reflect greater perceived stress)	Up to 9 months (follow-up)
Other	Suicidality	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.	Up to 9 months (follow-up; if participants report suicidal ideation when completing the IDS-SR or undergoing the M.I.N.I. interview)
Other	Hair cortisol (stress-related biomarker)	Long-term cortisol levels, assessed by hair samples collected pre - and post-treatment	Up to 12 weeks (post-treatment)
Other	Inflammatory markers (stress-related biomarkers)	Levels of C-reactive protein (CRP), Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-6 (IL-6), assessed by blood samples drawn pre - and post-treatment	Up to 12 weeks (post-treatment)
Other	Epigenetic markers (stress-related biomarkers)	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.	Up to 12 weeks (post-treatment)
Other	Brain structure - T1 (fMRI sub-study, not yet started, anticipated start April 2022)	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).	Up to 12 weeks (post-treatment)
Other	Brain structure - DTI (fMRI sub-study, not yet started, anticipated start April 2022)	White matter (WM) tract integrity will be investigated by acquiring diffusion tensor images.	Up to 12 weeks (post-treatment)
Other	Functional dynamics of spontaneous neural activity (fMRI sub-study, not yet started, anticipated start April 2022)	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)	Up to 12 weeks (post-treatment)
Other	Working memory (fMRI sub-study, not yet started, anticipated start April 2022)	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.	Up to 12 weeks (post-treatment)
Other	Emotion regulation (fMRI sub-study, not yet started, anticipated start April 2022)	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)	Up to 12 weeks (post-treatment)
Other	Reward Processing (fMRI sub-study, not yet started, anticipated start April 2022)	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)	Up to 12 weeks (post-treatment)
Primary	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)	Up to 12 weeks (post-treatment)
Secondary	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)	Up to 9 months (follow-up)
Secondary	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).	Up to 9 monts (follow-up)