Blood Biomarkers in Suicidal Behaviour

Major Depression Clinical Trial

— 2BSB  

Official title:

Modification of the Expression of ADARs and PDE8A Editing in Suicidal Behavior

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02855918
• Other study ID #: UF 9625
• Secondary ID: 2015-A01978-41
• Status: Completed
• Phase: N/A
• Start date: September 23, 2016
• Est. completion date: June 24, 2020

Study information

• Verified date: December 2021
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Suicidal behavior (SB) is a major public health problem in France, with more than 10,000 suicides and 220,000 suicide attempts per year.

According to the commonly accepted model for understanding suicidal behavior, individuals who carry a suicidal act when subjected to stress factors (environmental stress, depression, substance ...) are those which have a specific vulnerability.

These vulnerabilities can be considered as clinical parameters (propensity to despair, aggressive and/or impulsive traits), neurobiological parameters (dysfunction of the serotonergic system, ...) and cognitive parameters (taking disadvantageous decision ...). Suicidal vulnerability is partly underpinned by genetic factors. The interest of current researches is to identify biomarkers that will improve the opportunities for early identification of subject with a risk for SB. Numerous scientific studies, including post-mortem studies of the brains of suicide completers, have established a link between dysregulation of the ribonucleic acids editing (RNA) of certain genes, the enzymatic activity of Adenosine deaminases acting on RNA (ADARS) responsible for this edition and suicidal behavior. A prospective study is needed to quantify and qualify in the blood of depressed patients (with or without a history of suicide) and healthy controls, the editing changes and the expression and alteration of the activity of ADARS.

Description:

Over two years, 600 participants will be recruited:

• 225 subjects with current major depressive episode and an history of suicide attempt (depressed suicide attempters)

• 225 subjects with current major depressive episode but with no personal history of suicide attempt (affective controls)

• 150 subjects with no history of psychopathology whole life (healthy controls)

Each patient will attend a total of 3visits during a follow-up period of 6 months +/- 15 days (inclusion, visit at 3 and 6 months).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: June 24, 2020
• Est. primary completion date: June 24, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

No specific inclusion criteria :

• 18 to 65 years

• Subject who signed the informed consent

• Able to understand the nature, purpose and methodology of the study

• Able to understand and perform the clinical and neuropsychological evaluations.

Specific inclusion criteria depressed suicide attempters:

• Subject whose primary psychiatric diagnosis is a major depressive episode according to Diagnostic and Statistical Manual of Mental Disorders -5 (DSM-5) criteria

• Personal history of suicide attempt

affective controls:

• Subject whose primary psychiatric diagnosis is a major depressive episode according to DSM-5 criteria

• No personal history of suicide attempt

healthy controls:

• No personal history of psychiatric disorders (Axis I ) defined by the Mini International Neuropsychiatric Interview (MINI) according to the DSM-5 criteria

• No history of suicide attempt

Exclusion criteria

• Refusal of participation

• Deprived of liberty Subject (by judicial or administrative decision)

• Subject protected by law (guardianship)

• Subject exclusion period in relation to another protocol

• Subject is not affiliated to a social security scheme, beneficiary or not such a plan

• Subject for which the maximum annual amount of allowances of € 4,500 has been reached

• Pregnant women

• Breastfeeding Women

Related Conditions & MeSH terms

• Depressive Disorder, Major
• Major Depression

Intervention

Other:
• Blood sample for genetic purpose
All the participants will performed the same evaluations and blood analysis : A clinical assessment by psychiatrist Self report questionnaires for the assessment of a potential mood disorder and history of SB, moral/physical pain, personality traits… A neuropsychological assessment for the evaluations of cognitive performances A routine blood sampling to the realization of a standard blood test A specific blood sampling (PAXgene® tubes) to extract total RNA of blood cells and measure the expression of ADARS RNA and editing of the PDE8A transcript.

Locations

Country	Name	City	State
France	University Hospital	Montpêllier

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Montpellier	Institut National de la Santé Et de la Recherche Médicale, France, Sys2Diag, Mixt laboratory CNRS/Alcediag, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evolution of the modification of the expression of Adenosine deaminases acting on RNA (ADARs) and of the editing profile of phospho-diesterase 8A (PDE8A)	Studying ADARs expression and RNA editing of genes associated with SB, including PDE8A and comparison of these results between healthy controls and depressed patients with or without history of SB	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression of ADAR1a enzymes	Comparison of the profiles of ADARs expression and PDE8A editing between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Spindle And Kinetochore Associated protein 2 (SKA2)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression of ADAR1b enzymes	Comparison of the profiles of ADARs expression and PDE8A editing between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression of ADAR2 enzymes	Comparison of the profiles of ADARs expression and PDE8A editing between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Interleukins (ILs)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Chemokines (CXCLs)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Brain derived Neurotrphic factor (BDNF)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Cluster of differentiation 24 (CD24)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Three prime repair exonuclease 1 (TREX1)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Interferon stimulated gene 15 (ISG15)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Tumor necrosis factor alpha (TNF alpha)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Vascular endothelial growth factor (VEGF)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of Hydroxytryptamine receptor 2A (HTR2A)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion
Secondary	Modification of the expression and RNA editing of insulin-like growth factor protein 7 (IGFB7)	Comparison between non suicidal and suicidal depressed patients and healthy controls	At the inclusion visit, 3 months and 6 months after the inclusion