Biomarkers of ANTidepressant RESponse and Development Risk of Bipolar Disorder

NCT05568823 | Unknown

• 1 other identifier: 2020-51
• Study Type: interventional
• Target: 244
• Locations: 0 countries
• Sites: N/A

Brief Summary

One in five people will present a major depressive episode (MDE) in their lifetime. While antidepressants (ADs) are currently the standard treatment for MDE, the first AD prescribed is effective in less than 40% of patients and a complete clinical response is only observed after several weeks. Identifying early biomarkers of the response to treatment with an AD could allow the clinician to rapidly identify patients in whom treatment will not be effective and therefore modify patient care. We have recently shown that the messenger RNA (mRNA) of two proteins, ELK1 and GPR56, were present in different amounts in the blood cells of "responder" compared to those of "non-respondent" patients. In this context, our main objective will be to determine whether ELK1 and GPR56 mRNAs, are very early biomarkers of the response to AD, i.e., biomarkers whose variation precedes the clinical response by several weeks. Secondary objectives will be to identify early phase changes in neurophysiological measures, cognitive and behavioral tasks, as well as levels of blood coding and non-coding RNAs, serum cytokine, mitochondrial and metabolic markers, neuroimaging markers as biomarkers of differential treatment outcomes to antidepressant treatment. Patients will be treated with SERTRALINE or FLUOXETINE or DULOXETINE or MAPROTILINE (in monotherapy) with or without adjunct benzodiazepine. Patients are identified as responders or non-responders based on their clinical assessment at 8 weeks after treatment onset. In addition, a second stage will collect data to address another important issue for the management of patients with a MDE: to discriminate those with a major depressive disorder (MDD) from those with a bipolar disorder (BD). BD diagnosis is one of the most common reasons of failure to response to ADs. Therefore, one of our secondary objectives will be to identify biomarkers to differentiate between these two categories of patients. To do this, we will follow patients for a period of 24 months to identify those who will present during this follow-up the diagnostic criteria of bipolarity.

Conditions

Depression, Bipolar; Major Depressive Disorder; Bipolar Disorder

Outcome Measures

Primary Outcomes (1)

• Predictive value for antidepressant response of ELK1 mRNA levels or changes 3 days after AD start

  The area under the curve (AUC) value determined by receiving operating characteristic (ROC) analysis of ELK1 mRNA levels for the evolution of psychiatric symptoms following AD start, during a 8-weeks follow-up. Patients are identified as responders or nonresponders based on their clinical assessment

  8 weeks of treatment

Secondary Outcomes (5)

• Predictive value for antidepressant response of GPR56 and ELK1 mRNA levels at baseline, 3 days, 2 weeks or 8 weeks after AD start

  8 weeks of treatment

• Predictive value for antidepressant response of coding and non-coding (micro, circular, long non coding) RNA blood levels at baseline, 3 days, 2 weeks or 8 weeks after AD start

  8 weeks of treatment

• Predictive value for antidepressant response of serum cytokine concentration measured by immunoassay at baseline, 3 days, 2 weeks or 8 weeks, after AD start

  8 weeks of treatment

• Predictive value for antidepressant response of peripheral mitochondrial markers at baseline, 3 days 2 weeks or 8 weeks, after AD start Time Frame: 8 weeks of treatment

  8 weeks of treatment

• Predictive value for antidepressant response of MRI features

  8 weeks of treatment

Study Arms (2)

Patients "responding" to treatment after 8 weeks of treatment

OTHER

Patients "responding" to treatment after 8 weeks of treatment: i.e. whose clinical evolution is beneficial.

Other: Blood sampling

Patients "non-responding" to treatment after 8 weeks of treatment

OTHER

Patients "non-responding" to treatment after 8 weeks of treatment: i.e. whose clinical evolution is not satisfactory.

Other: Blood sampling

Interventions

Blood sampling OTHER

Measurement of markers of disease evolution

Also known as: Psychiatric survey, MRI Exam

Patients "non-responding" to treatment after 8 weeks of treatment; Patients "responding" to treatment after 8 weeks of treatment

Eligibility Criteria

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

You may qualify if:

• Male or female patient between 18 and 65 years of age
• Sufficient knowledge of the French language to complete the assessments
• Inpatients or outpatients with a major depressive episode (DSM-5 criteria);
• Score above 19 on the MADRS depression scale (moderate to severe depression);
• Without antidepressants, mood stabilizers or antipsychotics treatment or having stopped the previous medication(s) for more than 5 times the half-life of the prescribed treatment(s);

You may not qualify if:

• Patient with bipolar disorder, schizophrenia or psychotic disorder as defined by the DSM-5 and assessed by the MINI or any other pathology or treatment deemed clinically incompatible with the study by the investigator;
• Patient with moderate to severe substance use disorders (\>=4/11 criteria as defined in the DSM-5) and with the exception of smoking disorders
• Patient with pregnancy, unstable physiological condition or severe and symptomatic medical condition;
• Patient with a diagnosed neurological disorder affecting central nervous system function;
• Patient unable to give informed consent to participate in this study or unable to give the volunteer informed information;
• Patient who are not covered by a social security system;
• Patient under court protection or guardianship
• Patient who have received a vaccination within one month prior to initiation of treatment or who plan to be vaccinated within 2 weeks of initiation of treatment \> For patient undergoing MRI: presence of a contraindication for MRI examination.

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

MeSH Terms

Conditions

Bipolar Disorder; Depressive Disorder, Major

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Raoul BELZEAUX, MD

CONTACT

04 91 74 46 46; raoul.belzeaux@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Stratification on two groups of patients subsequently identified as responders or non-responders, after 8 weeks of treatment. Patients will be classified as responders or non-responders on the basis of the evolution of the MADRS depression scale score, i.e. an improvement of more than 50% in the intensity of symptoms between the beginning of the treatments and 8 weeks afterwards.

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 6, 2022
• Study Start: November 1, 2022
• Primary Completion: November 1, 2024
• Study Completion: January 2, 2025
• Last Updated: October 6, 2022

Record last verified: 2022-10