An observational study in Depressive Disorder, Major, Treatment Outcome and Cognitive Dysfunction, sponsored by Rigshospitalet, Denmark. Recruiting at 1 site in Denmark. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-10-08.
Sponsored by Rigshospitalet, Denmark · Observational
The BrainDrugs-D study uses multimodal neuroimaging combined with self-report measures, clinical and molecular markers to identify clinically relevant predictors that can identify subtypes of major depressive disorder (MDD) and, in a naturalistic setting, predict treatment response to standard antidepressive treatment. The cohorts are followed in nationwide health registries.
BrainDrugs-D is a cohort study of patients with major depressive disorder (MDD) who are deeply phenotyped with demographic, clinical, genetic, biochemical and neuroimaging modalities. These features are subsequently examined for their ability to identify subtypes of MDD and to predict treatment response.
Treatment and study population All participants are phenotyped before initiating a standardized 'treatment package' in out-patient clinics within the Mental Health Services in the Capital Region of Denmark. The goal is to recruit a total of 800 patients with non-psychotic MDD. We use broad inclusion criteria to enable recruitment of representative adult out-patients with non-psychotic MDD who receive standard treatment in practice.
As the study is designed with a high degree of ecological validity, it will not interfere with or delay the standard treatment package for depression. The treatment package is a national uniform package designed by Mental Health Services in the Capital Region, it has been in use since 2017, after several preceding years of clinical use and patient experience. Treatment for first-episode depression has a manualized group Cognitive-behavioural therapy (CBT) as the backbone: 2-3 hours of initial workup followed by 6 hours of individual therapy or 12 sessions of 2 hours of group therapy (8 patients per group), 1-2 hours of engagement and psychoeducation of relatives, 1-5 hours of medication clinic and 2 hours of relapse prevention. Antidepressant medication and individual psychotherapy are instituted, as needed.
Groups The study comprises three groups: The entire cohort (n=800) will have basic clinical, cognitive, psychometric, and biological data available. A subgroup (Subcohort I, n=600) provided expanded clinical, cognitive, psychometric, and biological data as well as Magnetic Resonance Imaging (MRI) and Electroencephalogram (EEG). Subcohort II, (n=60) will be exclusively for patients unmedicated at initiation, consisting of the same investigation, and contributing Positron Emission Tomography imaging with the [11C]-UCB-J tracer of synaptic density.
Follow-up All cohorts receive questionnaires assessing depression symptom severity, level of functioning, and QoL at the three follow-up time points. We also assess the side effects of psychological treatment and medication at the end of the treatment package. The cohorts are also followed in nationwide health registries.
Outcomes The primary outcome is remission (QIDS ≤5) and clinical improvement (≥50% reduction in QIDS) after 6 months.
Secondary endpoints include remission status 12 and 18 months after treatment start and change in QIDS, SCL10, WHO-5, and SDS scores from baseline to follow-ups.
Analysis We will use machine learning algorithms to determine a combination of baseline characteristics that best predict treatment outcomes and statistical models to investigate the association between individual and clinical outcomes. We will also assess associations between patient characteristics, treatment choices, and clinical outcomes using path analysis, enabling us to estimate the effect of treatment choices and timing on the clinical outcome.
Hypotheses for the whole cohort:
Primary hypotheses:
1.1 Clinical, cognitive, psychometric, genetic, and blood biomarker measures at inclusion can predict clinical remission (defined as QIDS≤5) at the first follow-up.
1.2 Clinical, cognitive, psychometric, genetic, and blood biomarker measures at inclusion can predict clinical improvement (a ≥50% reduction in QIDS from pretreatment) at the first follow-up.
Secondary hypotheses:
1.3 Composite scores across a range of clinical, cognitive, psychometric, genetic, and blood biomarker measures at inclusion can cluster patients into MDD subgroups associated with treatment trajectories and outcomes.
1.4 Clinical, cognitive, psychometric, genetic, and blood biomarker measures at inclusion are associated with clinical outcome defined as a change in QIDS.
1.5 Path analysis of baseline patient characteristics and treatment tracks can uncover causal paths for clinical improvements, i.e., estimate the effect of treatment on clinical outcomes.
Hypotheses for Subcohort I
Primary hypotheses:
2.1 MRI, fMRI, and EEG patterns at inclusion may be associated with depressive phenotypes.
2.2 Adding EEG, MRI, and fMRI measures at inclusion to the classifier model (defined in hypotheses 1.1 and 1.2) may significantly improve the prediction of clinical remission and improvement.
Secondary hypotheses:
2.3 Adding EEG, MRI, and fMRI measures at inclusion to the composite score (defined in hypothesis 1.3) may significantly improve the clustering of patients into MDD subgroups.
Hypotheses for Subcohort II
Primary hypotheses:
3.1 Cerebral [11C]-UCB-J binding is lower in patients with MDD than in healthy controls.
3.2 Domain-specific cognitive function correlates positively with [11C]-UCB-J binding in associated cortical and subcortical areas.
Secondary hypotheses:
3.1 Depression severity, anxiety, and anhedonia correlate with [11C]-UCB-J binding in associated cortical and subcortical areas.
3.2 Addition of [11C]-UCB-J binding, EEG, and MRI measures at inclusion to the composite score (defined in hypotheses 2.1) can significantly improve the prediction of clinical improvement and remission beyond clinical, cognitive, psychometric, fluid biomarker, EEG, and MRI measures in antidepressant naïve patients.
8,057 studies on the registry are indexed under Depression; 1,643 are open to participants now.
This study's planned enrollment of 800 is above the median of 160 across 1,084 observational studies indexed under Depression.
Browse Depression studies →Rigshospitalet, Denmark is the lead sponsor of 1,017 studies on the registry; 183 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The Capital Region of Denmark is the most urban area of Denmark and has a population of 1.6 million people. Patients in the Capital Region of Denmark are referred from their general practitioner or other treatment providers for treatment within the mental health services in the region. All six clinics in the region provide treatment packages for first-episode depression.
Exclusion Criteria:
Additional exclusion criteria for Cohort II:
Additional exclusion criteria for Cohort III:
All participants included will contribute with basic clinical, cognitive, psychometric, genetic and biochemical data.
Combination Product: Treatment Package for First-Episode Depression
Patients in Subcohort I undergo MRI and EEG in addition to expanded clinical, cognitive, psychometric, and biological data.
Combination Product: Treatment Package for First-Episode Depression
A subgroup of Subcohort I, including only patients who at inclusion do not receive any pharmacological treatment for their depression, undergo in addition Positron Emission Tomography imaging with \[11C\]-UCB-J for measurement of cerebral synaptic density.
Combination Product: Treatment Package for First-Episode Depression
The outpatient 'treatment package' for first episode depression is a national uniform package designed by Mental Health Services in the Capital Region. The treatment package for first-episode depression is a program with manualized group CBT, psychoeducation of patients and relatives, and relapse prevention. Antidepressant medication and individual psychotherapy are available as needed.
Clinical remission
Quick Inventory of Depressive Symptomatology (QIDS) score of ≤5
Time frame: Baseline to 6 months after treatment start
Clinical improvement
≥50% reduction in QIDS score.
Time frame: Baseline to 6 months after treatment start
Changes in depression severity
Changes in depression severity by QIDS (range from 0 to 27, higher score indicating greater severity)
Time frame: Baseline to 6, 12 and 18 months after treatment start
Changes in symptomatology
Changes on the Brief Symptom Inventory 18 (BSI-18, range 0-72, higher score indicating greater psychological distress)
Time frame: Baseline to 6, 12 and 18 months after treatment start
Changes in depression and anxiety symptomatology
Changes on the 10-item depression and anxiety symptom checklist (SCL-10, range 0-100 higher score indicating greater symptomatology)
Time frame: Baseline to 6, 12 and 18 months after treatment start
Change in wellbeing
Changes measured by the WHO-5 well-being Index (range 0-100, with 0 representing the worst imaginable well-being and 100 representing the best imaginable well-being).
Time frame: Baseline to 6, 12 and 18 months after treatment start
Change in disability
Changes measured by modified S. Disability Scale (mSDS) scores (range 0-30, with greater score indicating greater disability)
Time frame: Baseline to 6, 12 and 18 months after treatment start
Medication side-effects
Patient Reported Inventory of Side-Effects (PRISE)
Time frame: Baseline to 6 months after treatment start
Adverse and unwanted events in psychotherapy
Negative Effects Questionnaire (NEQ) to assess adverse and unwanted events in psychological treatment
Time frame: Baseline to 6 months after treatment start
Psychosocial remission
Defined as either a WHO-5 score of \>49, an SCL-10 score of \<26 or an mSDS score of \<10.
Time frame: Baseline to 6, 12 and 18 months after treatment start
Plan to share: Yes — Via the Center for Integrated Molecular Brain Imaging (Knudsen et al. 2016, NeuroImage), data will be available for the research community upon request and after approval by the scientific board at Neurobiological Research Unit. The data will be stored on a password-protected survey system behind secure "firewalls" per the General Data Protection Regulation (GDPR, Regulation European Union (EU) 2016/679 April 27th, 2016) and the Danish Data Protection Act and the regulation (Act No. 502 of May 23rd, 2018). Potential further processing in other national and international laboratories may occur, yet always per the GDPR (Regulation EU 2016/679 April 27th, 2016), the Danish Data Protection Act, and the regulation (Act No. 502 of May 23rd, 2018).
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Rigshospitalet, Denmark