Clinical Validation Study for EDIT-B Test: an Aid for Differential Diagnosis of Bipolar Disorder, Based on RNA Editing Blood Biomarkers

NCT05603819 | Completed

• 1 other identifier: EDIT-B
• Study Type: observational
• Target: 418
• Locations: 3 countries
• Sites: 4

Brief Summary

Differentiation between major depressive disorder (MDD) and bipolar disorder (BD) as soon as possible in the patient journey represents a major clinical issue. When the patient is in a depressive phase, the symptoms are similar between the two pathologies and the current clinical scales fail in distinguishing them. Physicians often report this difficulty and as a consequence, the mean time from onset to bipolar disorder diagnosis is currently 7.5 years. These diagnostic delays and misdiagnosis lead to damaging consequences for patients and their loved ones: worsening of symptoms, comorbidities, suicide risk and inadequate care resulting in severe impairment in social and occupational functioning. Faced with these high expectations for accurate diagnostic methods for an earlier management of psychiatric patients, the combination of relevant clinical features and biomarkers could stand for a solution, leading to a personalised approach in patients with mood disorders. In a first clinical discovery study, a panel of RNA biomarkers in the blood of patients with a major depressive episode (MDE) has been identified, allowing to differentiate bipolar disorder from MDD (unipolar depression). These biomarkers are based on RNA modifications, namely RNA editing, that could be identified using molecular biology, NGS and artificial intelligence. This panel constitutes EDIT-B test, which is based on Alcediag's proprietary and patented biomarkers and algorithms. The present study aims to validate the biomarker signatures proposed by Alcediag by measuring the association between the modifications of the RNA editing and major depressive disorder/ bipolar disorder diagnosis, in patients with a MDE in real-life setting pilot centres.

Conditions

Bipolar Disorder; Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Diagnostic performances of EDIT-B signatures on MDD vs. BD differentiation in patients with depression.

  The objective of this study is to estimate three EDIT-B signatures in term of their external validity. For this purpose, performances of the tests will be estimated by calculating for each signature its Sensitivity (i.e. the probability that a test will indicate 'bipolar disorders' among those with this disease), Specificity (i.e. the fraction of those without bipolar disorders who will have a negative test result) and its Accuracy to predict the diagnosis of bipolar disorders. In addition, Area under the ROC curves of each EDIT-B signature will be calculated. The categorisation of the type of disorder (MDD vs. BD) by experts will be based on the MINI considered as the gold standard for diagnosis. The performances of the tested signatures will be compared on a two-by-two basis by comparing sensitivities and specificity , using the methods based on Mac Nemar test proposed by Hawass. AUC-ROC of the 3 signatures will also be compared by DeLong method.

  Specimen collection needed for evaluation of diagnostic performances: 1 day (= 1 visit).

Study Arms (2)

Bipolar disorder

Patients with depression suffering from bipolar disorder.

Device: EDIT-B

Major depressive disorder

Patients with depression suffering from major depressive disorder.

Device: EDIT-B

Interventions

EDIT-B DEVICE

To perform EDIT-B test, questionnaires and 2x0.5 mL whole blood are collected from each patient.

Bipolar disorder; Major depressive disorder

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with depression meeting the MDE criteria in DSM-5 using the MINI will be eligible for the study. They can be in- and out-patients for each clinical center.

You may qualify if:

• Signed informed consent.
• MADRS ≥ 20
• In- and out-patients can be recruited.
• Diagnosed with MDE with the MINI for DSM-5
• Currently treated for the MDE
• Diagnosed with MDD or BD with the MINI for DSM-5.
• For patients with BD: at least one manic or hypomanic episode
• For patients with MDD: at least one MDE

You may not qualify if:

• MDD patients with first degree family history of bipolar disorder
• YMRS \> 12
• Pregnant women
• Unipolar or bipolar depression secondary to major central nervous system affections, including infections in the brain, tumours of the brain, stroke, Alzheimer's disease, Parkinson's disease, Multiple sclerosis, other major brain affections
• Schizo-affective patients
• Abbrevations:
• BD Bipolar Disorder DSM-5 Diagnostic and Statistical Manual of Mental disorders 5 MADRS Montgomery-Asberg Depression Rating Scale MDD Major Depressive Disorder MDE Major Depressive Episode MINI Mini-International Neuropsychiatric Interview YMRS Young Mania Rating Scale

Sponsors & Collaborators

• Alcediag: lead
• Hospital Clinic of Barcelona: collaborator
• Fundacion Clinic per a la Recerca Biomédica: collaborator
• Region Capital Denmark: collaborator
• GHU Paris Psychiatry & Neurosciences: collaborator
• Parc Sanitari Sant Joan de Déu: collaborator
• Fundació Sant Joan de Déu: collaborator
• Synlab Italie: collaborator

Study Sites (4)

The Capital Region of Denmark

Copenhagen, 2100, Denmark

Location

GHU Paris Psychiatrie & Neurosciences

Paris, 75014, France

Location

Parc Sanitari Sant Joan de Déu

Sant Boi de Llobregat, Barcelona, 08830, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

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Biospecimen

Retention: SAMPLES WITH DNA

Whole blood samples (2x0.5 mL) stored in PAXgene RNA collection tubes.

MeSH Terms

Conditions

Bipolar Disorder; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Depressive Disorder

Study Officials

• Eduard Vieta

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2022
• First Posted: November 3, 2022
• Study Start: June 29, 2022
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: December 17, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); FR (1); ES (2)