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Effect of Genetic Alterations in Key Genes in the Kynurenine Pathway on Suicidal Behavior (SuiKYN)

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ClinicalTrials.gov Identifier: NCT04565834
Recruitment Status : Recruiting
First Posted : September 25, 2020
Last Update Posted : September 25, 2020
Sponsor:
Collaborator:
Universidad Autonoma de Madrid
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes

Brief Summary:
Current research has shown that an imbalance in the Kinurenine pathway plays a role in the physiopathology of neurogenerative and mental disorders (with a decrease in neuroprotective metabolites and an increase in neurotoxic products). So far the research has concentrated on the enzymes IDO, KAT, KMO, 3HAO and QPRT which are the key players in this pathway. Several polymorphisms affecting these enzymes have been associated with certain disorders characterized by a deregulation of the inflammation and immune response (McCauley et al 2009,Tardito et al 2013, Lee et al 2014), but no studies have ever tried to find a link between these enzymes and suicidal behavior. The investigators hypothesize that people who have attempted to commit suicide will have pro-inflammatory genetic variations affecting the kynurenine pathway.

Condition or disease Intervention/treatment
Kynureninase Polymorphism Suicidal Behavior Genetic: Analysis of Single nucleotide polymorphisms in each group.

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Study Type : Observational
Estimated Enrollment : 525 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: A Study on Genetic Alterations (Polymorphism) in Key Genes in the Kynurenine Pathway on Suicidal Behavior
Actual Study Start Date : December 1, 2019
Estimated Primary Completion Date : March 1, 2022
Estimated Study Completion Date : September 1, 2022

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Suicidal patients
Patients who have made at least one attempt to commit suicide.
Genetic: Analysis of Single nucleotide polymorphisms in each group.
The 6 single nucleotide polymorphisms (SNPs) determined will then be genotyped according to the Thermofisher Taqman technique ona 480 LightCycler (Roche Applied Science). 10% of the genotypes will be confirmed via Sanger sequencing on a 3500xl Thermofisher sequencer according to the manufacturer's recommendations.
Other Name: Determination of frequency of IDO1 rs 9657182, IDO1 rs35059413, IDO2 rs2929115, IDO2 rs2929116, KMO rs1053230, KMO rs2275163 for each group of patients.

Control group

This group will consist of two types of people:

  • 75 healthy subjects (i.e. those who have no mental disorders and have never attempted to commit suicide) and
  • 150 patients suffering from depression but have never attempted to commit suicide.
Genetic: Analysis of Single nucleotide polymorphisms in each group.
The 6 single nucleotide polymorphisms (SNPs) determined will then be genotyped according to the Thermofisher Taqman technique ona 480 LightCycler (Roche Applied Science). 10% of the genotypes will be confirmed via Sanger sequencing on a 3500xl Thermofisher sequencer according to the manufacturer's recommendations.
Other Name: Determination of frequency of IDO1 rs 9657182, IDO1 rs35059413, IDO2 rs2929115, IDO2 rs2929116, KMO rs1053230, KMO rs2275163 for each group of patients.




Primary Outcome Measures :
  1. Presence of single nucleotide polymorphism rs9657182 of Enzyme IDO1 in the Suicide group [ Time Frame: 24 months ]
    The presence of this genetic variation will be measured as a percentage

  2. Presence of single nucleotide polymorphism rs9657182 of Enzyme IDO1 in the Emotion Control group [ Time Frame: 24 months ]
    The presence of this genetic variation will be measured as a percentage


Secondary Outcome Measures :
  1. A. Frequency of single nucleotide polymorphism rs35059413 of Enzyme IDO1 in the Suicide group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  2. A. Frequency of single nucleotide polymorphism rs35059413 of Enzyme IDO1 in the Emotion Control group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  3. A. Frequency of single nucleotide polymorphism rs2929115 of Enzyme IDO2 in the Suicide group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  4. A. Frequency of single nucleotide polymorphism rs2929115 of Enzyme IDO2 in the Emotion Control group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  5. A. Frequency of single nucleotide polymorphism rs2929116 of Enzyme IDO2 in the Suicide group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  6. A. Frequency of single nucleotide polymorphism rs2929116 of Enzyme IDO2 in the Emotion Control group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  7. A. Frequency of single nucleotide polymorphism rs1053230 of KMO in the Suicide group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  8. A. Frequency of single nucleotide polymorphism rs1053230 of KMO in the Emotion Control group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  9. A. Frequency of single nucleotide polymorphism rs2275163 of KMO in the Suicide group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  10. A. Frequency of single nucleotide polymorphism rs2275163 of KMO in the Emotion Control group [ Time Frame: 24 months ]
    The frequency of this genetic variation will be measured as a percentage

  11. B. Simultaneous influence of the various single nucleotide polymorphisms on the functioning of the kynurenine pathway and suicidal behavior. [ Time Frame: 24 months ]
    The numerical value of the polygenic risk score will be used to measure this criterion.

  12. C. Percentage frequency of single nucleotide polymorphisms among patients in the Suicide group. [ Time Frame: 24 months ]
    The frequency of single nucleotide polymorphisms, measured as a percentage, will be compared with the number of suicide attempts, the lethality, the method used and the intensity of suicidal ideation in the Suicide group. The polygenic risk score is calculated as a weighted sum of the risk alleles resulting from the study using GWAS (genome-wide association study) summary statistics data. This score is not calculated on a scale but as a relative risk compared to the unaffected population.

  13. D. Correlation between negative life events triggering suicide attempts and the level of inflammation in the Suicide group. [ Time Frame: 24 months ]
    Inflammation will be measured according to the level of the main pro-inflammatory cytokines in the various samples : TGF-beta. The rate of anti-inflammatory cytokines IL-2 and IL-4 will also be measured in pg/ml and mg/ml

  14. D. Correlation between negative life events triggering suicide attempts and the level of inflammation in the Affective Controls group. [ Time Frame: 24 months ]
    Inflammation will be measured according to the level of the main pro-inflammatory cytokines in the various samples : TGF-beta. The rate of anti-inflammatory cytokines IL-2 and IL-4 will also be measured in pg/ml and mg/ml


Other Outcome Measures:
  1. Frequency of rs35059413 of IDO1 involved in the kynurenine pathway in the Suicide group [ Time Frame: 24 months ]
    The frequency of rs35059413 of IDO1 involved in the kynurenine pathway in the suicide group will be measured as a percentage.

  2. Frequency of rs35059413 of IDO1 involved in the kynurenine pathway in the Healthy Control group [ Time Frame: 24 months ]
    The frequency of rs35059413 of IDO1 involved in the kynurenine pathway in the healthy controls group will be measured as a percentage.

  3. Frequency of rs2929115 of IDO2 involved in the kynurenine pathway in the Suicide group [ Time Frame: 24 months ]
    The frequency of rs2929115 of IDO2 involved in the kynurenine pathway in the suicide group will be measured as a percentage

  4. Frequency of rs2929115 of IDO2 involved in the kynurenine pathway in the Healthy Controls group [ Time Frame: 24 months ]
    The frequency of rs2929115 of IDO2 involved in the kynurenine pathway in the healthy controls group will be measured as a percentage

  5. Frequency of rs2929116 of IDO2 involved in the kynurenine pathway in the Suicide group [ Time Frame: 24 months ]
    The frequency of rs2929116 of IDO2 involved in the kynurenine pathway in the suicide group will be measured as a percentage

  6. Frequency of rs2929116 of IDO2 involved in the kynurenine pathway in the Healthy Controls group [ Time Frame: 24 months ]
    The frequency of rs2929116 of IDO2 involved in the kynurenine pathway in the Affective Control group will be measured as a percentage

  7. Frequency of rs1053230 of KMO involved in the kynurenine pathway in the Suicide group [ Time Frame: 24 months ]
    The frequency of rs1053230 of KMO involved in the kynurenine pathway in the suicide group will be measured as a percentage

  8. Frequency of rs1053230 of KMO involved in the kynurenine pathway in the Healthy Controls group [ Time Frame: 24 months ]
    The frequency of rs1053230 of KMO involved in the kynurenine pathway in the healthy controls group will be measured as a percentage

  9. Frequency of rs2275163 of KMO involved in the kynurenine pathway in the Suicide group [ Time Frame: 24 months ]
    The frequency of rs2275163 of KMO involved in the kynurenine pathway in the suicide group will be measured as a percentage

  10. Frequency of rs2275163 of KMO involved in the kynurenine pathway in the Healthy Controls group [ Time Frame: 24 months ]
    The frequency of rs2275163 of KMO involved in the kynurenine pathway in the healthy controls group will be measured as a percentage

  11. Age of patients in the Suicide group [ Time Frame: 24 months ]
    The age of patients in the suicide group will be recorded for statistical purposes

  12. Age of patients in the Healthy Controls group [ Time Frame: 24 months ]
    The age of patients in the healthy controls group will be recorded for statistical purposes

  13. Weight of patients in the Suicide group [ Time Frame: 24 months ]
    The weight of patients in the suicide group will be recorded in kg for statistical purposes

  14. Weight of patients in the Healthy Controls group [ Time Frame: 24 months ]
    The weight of patients in the healthy controls group will be recorded in kg for statistical purposes

  15. Height of patients in the Suicide group [ Time Frame: 24 months ]
    The height of patients in the suicide group will be recorded in centimeters for statistical purposes

  16. Height of patients in the Healthy Controls group [ Time Frame: 24 months ]
    The height of patients in the healthy controls group will be recorded in centimeters for statistical purposes

  17. Gender of patients in the Suicide group [ Time Frame: 24 months ]
    The gender of patients in the suicide group will be recorded for statistical purposes

  18. Gender of patients in the Healthy Controls group [ Time Frame: 24 months ]
    The gender of patients in the healthy controls group will be recorded for statistical purposes

  19. Gene frequency of patients in the Suicide group [ Time Frame: 24 months ]
    The gene frequency of patients in the suicide group will be recorded as a percentage for statistical purposes

  20. Gene frequency of patients in the Healthy Controls group [ Time Frame: 24 months ]
    The gene frequency of patients in the healthy controls group will be recorded as a percentage for statistical purposes

  21. Cytokine concentration: patients in the Suicide group [ Time Frame: 24 months ]
    The cytokine concentration of patients in the suicide group will be recorded in pg/l

  22. Cytokine concentration: patients in the Healthy Controls group [ Time Frame: 24 months ]
    The cytokine concentration of patients in the healthy controls group will be recorded in pg/l


Biospecimen Retention:   Samples With DNA
These are biological samples collected from previous registered studies (SUI-PREDICT, SMART CRISIS, SPAD) as well as samples from the Human Molecular Genetics Laboratory A-209 from the Faculty of Biology at the Independent University of Madrid, Spain.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
All patients for whom biological samples have been collected and registered in the hospital's databank for the purpose of previously registered studies : SPAD (RCB no. 2016-A01375-46), SMART-CRISIS (RCB no.: 2017-A02634-49) and SUI-PREDICT (RCB no.: 2016-A00845-46) and several studies conducted at the university hospitals of Puerta de Hierro, Ramon y Cajal et Fundacion Jiminez Diaz in Madrid, Spain, since 2004.
Criteria

Inclusion Criteria:

  • For the "Suicide" group: Any patient aged 18 or over who has made at least one suicide attempt.
  • For the control group: Any patient aged 18 or over, suffering from depression but has never attempted to commit suicide and any healthy patient who has never had any mental disorders.

Exclusion Criteria:

  • Any patient who has expressed opposition to the use of his/her data.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04565834


Contacts
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Contact: Jorge LOPEZ-CASTROMAN, Professor +33466683897 Jorge.lopezcastroman@chu-nimes.fr
Contact: Anissa MEGZARI +33 4 66 68 42 36 drc@chu-nimes.fr

Locations
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France
Centre Hospitalier Universitaire de Nîmes Recruiting
Nîmes, Gard, France, 30029
Contact: Jorge Lopez-Castroman, Professor    +33466683897    Jorge.lopezcastroman@chu-nimes.fr   
Spain
José-Fernandez-Piqueras Recruiting
Madrid, Spain, 28049
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
Universidad Autonoma de Madrid
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Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT04565834    
Other Study ID Numbers: NIMAO/2019-2/JLC-01
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: September 25, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier Universitaire de Nīmes:
Suicide
Inflammation
Kynurenine