Precision Medicine in the Depression Treatment

NCT ID: NCT05616559

Last Updated: 2024-10-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

800 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-06-15

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Depressive Disorder, Major Treatment Outcome Cognitive Dysfunction Cognitive Behavioral Therapy Antidepressive Agents

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Patient cohort (n=800)

All participants included will contribute with basic clinical, cognitive, psychometric, genetic and biochemical data.

Treatment Package for First-Episode Depression

Intervention Type COMBINATION_PRODUCT

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.

Subcohort I (n=600)

Patients in Subcohort I undergo MRI and EEG in addition to expanded clinical, cognitive, psychometric, and biological data.

Treatment Package for First-Episode Depression

Intervention Type COMBINATION_PRODUCT

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.

Subcohort II - drug naive PET subgroup (n=60)

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.

Treatment Package for First-Episode Depression

Intervention Type COMBINATION_PRODUCT

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.

Interventions

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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.

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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Inclusion Criteria

* Age between 18 and 65 years
* Fulfilment of International Classification of Diseases version 10 diagnostic criteria for a primary depressive episode (i.e., not secondary to known organic or other psychiatric disorder).
* Referral to a treatment package for single-episode depression.

Exclusion Criteria

* Psychosis or psychotic symptoms
* History of severe head trauma
* Somatic disease associated with morphological brain changes (e.g., brain tumour)
* Insufficient Danish language skills to complete questionnaires and cognitive testing


* Severe somatic disease
* Contraindications for MRI (e.g., metal implants, claustrophobia or back problems)


* Severe somatic disease
* Contraindications for MRI
* Exposure to radioactivity \>10 mSv within the last year
* Pregnancy or breastfeeding
* Use of psychotropic drugs
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mental Health Services in the Capital Region, Denmark

OTHER

Sponsor Role collaborator

Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak

OTHER

Sponsor Role collaborator

Lundbeck Foundation

OTHER

Sponsor Role collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role lead

Responsible Party

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Gitte Moos Knudsen

MD,Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Martin B Jørgensen, DMSc

Role: PRINCIPAL_INVESTIGATOR

Psychiatric Center Copenhagen

Gitte MK Knudsen, DMSc

Role: STUDY_DIRECTOR

Neurobiology Research Unit, Rigshospitalet

Locations

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Neurobiology Research Unit, Rigshospitalet

Copenhagen, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Kristian HR Jensen, MD

Role: CONTACT

+45 35456720

Martin B Jørgensen, DMSc

Role: CONTACT

+45 38647082

Facility Contacts

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Gitte M Knudsen, Professor

Role: primary

+45 3545 6712

References

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Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JPT, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JPA, Geddes JR. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018 Apr 7;391(10128):1357-1366. doi: 10.1016/S0140-6736(17)32802-7. Epub 2018 Feb 21.

Reference Type BACKGROUND
PMID: 29477251 (View on PubMed)

Trevino K, McClintock SM, McDonald Fischer N, Vora A, Husain MM. Defining treatment-resistant depression: a comprehensive review of the literature. Ann Clin Psychiatry. 2014 Aug;26(3):222-32.

Reference Type BACKGROUND
PMID: 25166485 (View on PubMed)

Kessler RC, van Loo HM, Wardenaar KJ, Bossarte RM, Brenner LA, Ebert DD, de Jonge P, Nierenberg AA, Rosellini AJ, Sampson NA, Schoevers RA, Wilcox MA, Zaslavsky AM. Using patient self-reports to study heterogeneity of treatment effects in major depressive disorder. Epidemiol Psychiatr Sci. 2017 Feb;26(1):22-36. doi: 10.1017/S2045796016000020. Epub 2016 Jan 26.

Reference Type BACKGROUND
PMID: 26810628 (View on PubMed)

Jensen KHR, Dam VH, Ganz M, Fisher PM, Ip CT, Sankar A, Marstrand-Joergensen MR, Ozenne B, Osler M, Penninx BWJH, Pinborg LH, Frokjaer VG, Knudsen GM, Jorgensen MB. Deep phenotyping towards precision psychiatry of first-episode depression - the Brain Drugs-Depression cohort. BMC Psychiatry. 2023 Mar 9;23(1):151. doi: 10.1186/s12888-023-04618-x.

Reference Type DERIVED
PMID: 36894940 (View on PubMed)

Related Links

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Other Identifiers

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H-20083013

Identifier Type: -

Identifier Source: org_study_id

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