Genetic Susceptibility to Listeriosis

Listeriosis Clinical Trial

— Listeria-GEN  

Official title:

Genetic Susceptibility to Listeriosis - Listeria-GEN

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03357536
• Other study ID #: 2014-31
• Secondary ID: ID-RCB number :
• Status: Recruiting
• Phase: N/A
• Start date: November 28, 2017
• Est. completion date: November 30, 2027

Study information

• Verified date: January 2024
• Source: Institut Pasteur
• Contact: Marc Lecuit
• Phone: +33 1 40 61 34 20
• Email: marc.lecuit[@]pasteur.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Listeriosis is a rare, severe foodborne infection, responsible for severe invasive infections. It occurs in the great majority of cases in elderly patients and / or patients with comorbidities, with a deficit of innate or cellular immunity. Pregnancy is also a risk factor.

The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA) is an ongoing national case-control prospective study on listeriosis implemented since 2009 to study risk and prognosis factors for listeriosis. In this cohort, which enrolled 902 patients on 1 August 2014, 7% of patients with neurolisteriosis are under 40 years of age and have no identified risk factor. Genetic susceptibility is suspected in these patients. Genetic susceptibility could also explain the inconstant development of a neurolisteriosis or fetal infection, as well as the particular severity of some infections (death, foetal loss, neurological sequelae).

The aim of the study is to identify genetic susceptibility to Listeriosis.

Description:

Listeriosis is a rare, severe foodborne infection caused by the bacterium Listeria monocytogenes (Lm), responsible for severe invasive infections. It occurs in the great majority of cases in elderly patients and / or patients with comorbidities, with a deficit of innate or cellular immunity. Pregnancy is also a risk factor.

The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA) is an ongoing national case-control prospective study on listeriosis implemented since 2009 to study risk and prognosis factors for listeriosis. In this cohort, which enrolled 902 patients on 1 August 2014, 7% of patients with neurolisteriosis are under 40 years of age and have no identified risk factor. Genetic susceptibility is suspected in these patients. Genetic susceptibility could also explain the inconstant development of a neurolisteriosis or fetal infection, as well as the particular severity of some infections (death, foetal loss, neurological sequelae).

The analysis of the genetically transmitted vulnerability of Lm has not yet been studied, because of the lack of accessibility to prospective cohorts (and their DNA) for this rare and severe infection.

The aim of the study is to identify genetic susceptibility to Listeriosis that will optimize the patient care in terms of treatment and prevention.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 30, 2027
• Est. primary completion date: November 30, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria for patients with Listeriosis :

• Microbiologically documented Listeriosis (either a severe form of listeriosis, or an atypical form of listeriosis, or less than 40 years old and without any co-morbidity identified)

• Affiliated or beneficiary of a social security system

• Informed and written consent

Inclusion Criteria for volunteers related to patients with Listeriosis (after identifying a genetic susceptibility in the patient with Listeriosis) :

• defined as father, mother, brother (s), sister (s), child (ren), grandparent (s), uncle (s), aunt (s), cousin (s), nephew (s), niece (s).

• Affiliated or beneficiary of a social security system

• Informed and written consent

Exclusion Criteria for volunteers related to patients with Listeriosis:

• Inability to consent

Related Conditions & MeSH terms

• Genetic Predisposition to Disease
• Listeriosis

Intervention

Procedure:
• Human biological samples
Blood sample Skin biopsy Saliva

Locations

Country	Name	City	State
France	Centre Médical de l'Institut Pasteur	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut Pasteur	Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of a susceptibility factor associated with Listeriosis infection	In patients with Listeriosis, the hypothesis that the identified genetic variation is the mutation responsible for the infection will be verified : by verifying that it is not a listed polymorphism by sequencing genomic DNA controls; by verifiyng that family genetic segregation is compatible with clinical segregation; by verifying the function of the mutated protein in the patient's cell lines and / or fresh cells; by performing complementation experiments by transfecting the wild-type allele into the patient's cells	10 years
Secondary	Identification of a susceptibility factor associated with the most severe or atypical forms	In patients with Listeriosis, the susceptibility factor associated with the most severe or atypical forms will be characterized : By testing the response and production of cytokines involved in infection control.; By identifying chromosomal regions associated with the disease by a homozygosity mapping genetic study on multiplex and / or inbred families.; By sequencing the identified candidate genes.	10 years