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
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).
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) |
Country | Name | City | State |
---|---|---|---|
Netherlands | GGZ inGeest | Amsterdam | Noord-Holland |
Netherlands | Altrecht | Utrecht | |
Netherlands | HSK Groep | Woerden | Utrecht |
Lead Sponsor | Collaborator |
---|---|
Amsterdam UMC, location VUmc | Altrecht, HSK Groep B.V., Stichting tot steun VCVGZ |
Netherlands,
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
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) |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05537558 -
Precision Medicine for the Prediction of Treatment (PROMPT) Response (PROMPT)
|
||
Terminated |
NCT02192099 -
Open Label Extension for GLYX13-C-202, NCT01684163
|
Phase 2 | |
Completed |
NCT03142919 -
Lipopolysaccharide (LPS) Challenge in Depression
|
Phase 2 | |
Recruiting |
NCT05547035 -
Identification of Physiological Data by a Wearable Monitor in Subjects Suffering From Major Depression Disorders
|
N/A | |
Terminated |
NCT02940769 -
Neurobiological Effects of Light on MDD
|
N/A | |
Recruiting |
NCT05892744 -
Establishing Multimodal Brain Biomarkers for Treatment Selection in Depression
|
Phase 4 | |
Recruiting |
NCT05537584 -
SMART Trial to Predict Anhedonia Response to Antidepressant Treatment
|
Phase 4 | |
Active, not recruiting |
NCT05061706 -
Multicenter Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
|
Phase 3 | |
Completed |
NCT04479852 -
A Study of the Safety and Efficacy of SP-624 in the Treatment of Adults With Major Depressive Disorder
|
Phase 2 | |
Recruiting |
NCT04032301 -
Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans
|
Phase 1 | |
Recruiting |
NCT05527951 -
Enhanced Measurement-Based Care Effectiveness for Depression (EMBED) Study
|
N/A | |
Completed |
NCT03511599 -
Cycloserine rTMS Plasticity Augmentation in Depression
|
Phase 1 | |
Recruiting |
NCT04392947 -
Treatment of Major Depressive Disorder With Bilateral Theta Burst Stimulation
|
N/A | |
Recruiting |
NCT05895747 -
5-HTP and Creatine for Depression R33 Phase
|
Phase 2 | |
Recruiting |
NCT05273996 -
Predictors of Cognitive Outcomes in Geriatric Depression
|
Phase 4 | |
Recruiting |
NCT05813093 -
Interleaved TMS-fMRI in Ultra-treatment Resistant Depression
|
N/A | |
Recruiting |
NCT05135897 -
The Neurobiological Fundaments of Depression and Its Relief Through Neurostimulation Treatments
|
||
Enrolling by invitation |
NCT04509102 -
Psychostimulant Augmentation of Repetitive TMS for the Treatment of Major Depressive Disorder
|
Early Phase 1 | |
Recruiting |
NCT06145594 -
EMA-Guided Maintenance TMS for Depression
|
N/A | |
Recruiting |
NCT06026917 -
Assessing Dopamine Transporter Occupancy in the Patients With Depression Brain With Toludesvenlafaxine Hydrochloride Extended-Release Tablets Using 11C-CFT Positron Emission Tomography (PET)
|
Phase 4 |