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

Suicidal Behavior Clinical Trial

— SuiKYN  

Official title:

A Study on Genetic Alterations (Polymorphism) in Key Genes in the Kynurenine Pathway on Suicidal Behavior

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04565834
• Other study ID #: NIMAO/2019-2/JLC-01
• Status: Recruiting
• Start date: December 1, 2019
• Est. completion date: September 1, 2022

Study information

• Verified date: January 2022
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: Jorge LOPEZ-CASTROMAN, Professor
• Phone: +33466683897
• Email: Jorge.lopezcastroman[@]chu-nimes.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 525
• Est. completion date: September 1, 2022
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Kynureninase
• Polymorphism
• Suicidal Behavior

Intervention

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.

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Nîmes	Nîmes	Gard
Spain	José-Fernandez-Piqueras	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes	Universidad Autonoma de Madrid

Countries where clinical trial is conducted

France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency of rs35059413 of IDO1 involved in the kynurenine pathway in the Suicide group	The frequency of rs35059413 of IDO1 involved in the kynurenine pathway in the suicide group will be measured as a percentage.	24 months
Other	Frequency of rs35059413 of IDO1 involved in the kynurenine pathway in the Healthy Control group	The frequency of rs35059413 of IDO1 involved in the kynurenine pathway in the healthy controls group will be measured as a percentage.	24 months
Other	Frequency of rs2929115 of IDO2 involved in the kynurenine pathway in the Suicide group	The frequency of rs2929115 of IDO2 involved in the kynurenine pathway in the suicide group will be measured as a percentage	24 months
Other	Frequency of rs2929115 of IDO2 involved in the kynurenine pathway in the Healthy Controls group	The frequency of rs2929115 of IDO2 involved in the kynurenine pathway in the healthy controls group will be measured as a percentage	24 months
Other	Frequency of rs2929116 of IDO2 involved in the kynurenine pathway in the Suicide group	The frequency of rs2929116 of IDO2 involved in the kynurenine pathway in the suicide group will be measured as a percentage	24 months
Other	Frequency of rs2929116 of IDO2 involved in the kynurenine pathway in the Healthy Controls group	The frequency of rs2929116 of IDO2 involved in the kynurenine pathway in the Affective Control group will be measured as a percentage	24 months
Other	Frequency of rs1053230 of KMO involved in the kynurenine pathway in the Suicide group	The frequency of rs1053230 of KMO involved in the kynurenine pathway in the suicide group will be measured as a percentage	24 months
Other	Frequency of rs1053230 of KMO involved in the kynurenine pathway in the Healthy Controls group	The frequency of rs1053230 of KMO involved in the kynurenine pathway in the healthy controls group will be measured as a percentage	24 months
Other	Frequency of rs2275163 of KMO involved in the kynurenine pathway in the Suicide group	The frequency of rs2275163 of KMO involved in the kynurenine pathway in the suicide group will be measured as a percentage	24 months
Other	Frequency of rs2275163 of KMO involved in the kynurenine pathway in the Healthy Controls group	The frequency of rs2275163 of KMO involved in the kynurenine pathway in the healthy controls group will be measured as a percentage	24 months
Other	Age of patients in the Suicide group	The age of patients in the suicide group will be recorded for statistical purposes	24 months
Other	Age of patients in the Healthy Controls group	The age of patients in the healthy controls group will be recorded for statistical purposes	24 months
Other	Weight of patients in the Suicide group	The weight of patients in the suicide group will be recorded in kg for statistical purposes	24 months
Other	Weight of patients in the Healthy Controls group	The weight of patients in the healthy controls group will be recorded in kg for statistical purposes	24 months
Other	Height of patients in the Suicide group	The height of patients in the suicide group will be recorded in centimeters for statistical purposes	24 months
Other	Height of patients in the Healthy Controls group	The height of patients in the healthy controls group will be recorded in centimeters for statistical purposes	24 months
Other	Gender of patients in the Suicide group	The gender of patients in the suicide group will be recorded for statistical purposes	24 months
Other	Gender of patients in the Healthy Controls group	The gender of patients in the healthy controls group will be recorded for statistical purposes	24 months
Other	Gene frequency of patients in the Suicide group	The gene frequency of patients in the suicide group will be recorded as a percentage for statistical purposes	24 months
Other	Gene frequency of patients in the Healthy Controls group	The gene frequency of patients in the healthy controls group will be recorded as a percentage for statistical purposes	24 months
Other	Cytokine concentration: patients in the Suicide group	The cytokine concentration of patients in the suicide group will be recorded in pg/l	24 months
Other	Cytokine concentration: patients in the Healthy Controls group	The cytokine concentration of patients in the healthy controls group will be recorded in pg/l	24 months
Primary	Presence of single nucleotide polymorphism rs9657182 of Enzyme IDO1 in the Suicide group	The presence of this genetic variation will be measured as a percentage	24 months
Primary	Presence of single nucleotide polymorphism rs9657182 of Enzyme IDO1 in the Emotion Control group	The presence of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs35059413 of Enzyme IDO1 in the Suicide group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs35059413 of Enzyme IDO1 in the Emotion Control group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs2929115 of Enzyme IDO2 in the Suicide group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs2929115 of Enzyme IDO2 in the Emotion Control group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs2929116 of Enzyme IDO2 in the Suicide group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs2929116 of Enzyme IDO2 in the Emotion Control group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs1053230 of KMO in the Suicide group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs1053230 of KMO in the Emotion Control group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs2275163 of KMO in the Suicide group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	A. Frequency of single nucleotide polymorphism rs2275163 of KMO in the Emotion Control group	The frequency of this genetic variation will be measured as a percentage	24 months
Secondary	B. Simultaneous influence of the various single nucleotide polymorphisms on the functioning of the kynurenine pathway and suicidal behavior.	The numerical value of the polygenic risk score will be used to measure this criterion.	24 months
Secondary	C. Percentage frequency of single nucleotide polymorphisms among patients in the Suicide group.	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.	24 months
Secondary	D. Correlation between negative life events triggering suicide attempts and the level of inflammation in the Suicide group.	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	24 months
Secondary	D. Correlation between negative life events triggering suicide attempts and the level of inflammation in the Affective Controls group.	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	24 months