ListeriosisMONALISAGENBIONCT02924220
Genetic Susceptibility and Biomarkers in Listeriosis
An observational study of Listeriosis, run by Institut Pasteur at 1 site in France.
Trial summary
Listeriosis is a rare, severe foodborne infection caused by the bacterium Listeria monocytogenes (Lm). It manifests as septicemia, central nervous system (CNS) infection and maternal-fetal (MF) infection. Its associated overall mortality is very high, above of 30%. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Listeriosis
- How many people
- 1,080 participants
- Where
- 1 siteFrance
- Study dates
- 16 Feb 2017to 30 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: All patients already recruited in the MONALISA study will be included. The MONALISA study is the first prospective case-control study focused on invasive listeriosis. Cases are patients with culture-proven listeriosis. Controls are patients without listeriosis but compatible clinical presentation.
Who may be able to join
- All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses.
Who cannot join
- Patients included in the MONALISA cohort without biological sample available.
Trial locations and contacts
1 site in 1 country.
France1 site
Institut Pasteur, Unité de Biologie des Infections
Paris, 75724 Cedex 15
About this study
Official title: Genetic Susceptibility and Biomarkers in Listeriosis (MONALISA-GENBIO)
Listeriosis is a rare, severe foodborne infection caused by the bacterium Listeria monocytogenes (Lm). It manifests as septicemia, central nervous system (CNS) infection and maternal-fetal (MF) infection. Its associated overall mortality is very high, above of 30%. A better knowledge on the factors involved in its occurrence and in clinical manifestations is therefore needed to improve outcome.
A number of frequent acquired risk factors for listeriosis have been identified, such as pregnancy, diabetes, cancer, HIV infection, and immunosuppressive therapies. However, no genetic study on host susceptibility to listeriosis in humans has been performed so far, in the absence of prospective collection of patients' samples. Also, listeriosis diagnosis is based on Lm culture from clinical samples. This method lacks sensitivity, and the contribution of biomarkers to listeriosis diagnosis and prognosis has not been evaluated.
Read more
The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA), is the first national case-control prospective study on listeriosis. It is implemented since 2009 and enrolls all culture-proven cases declared to the NRCL: and collects for each patient clinical and biological data and biological samples. Controls with comparable background and presentation are also included. 818 cases have been included (427 S, 252 CNS and 107 MN) over 3.5 years, along with 456 controls.
The aim of the study is to identify human genetic susceptibility factors to listeriosis, biomarkers to improve its diagnosis and prognosis (survival or death), and thereby help improve management of patients with listeriosis.
Samples from the completed cohort will be analyzed : SNPs genotyping and exam sequencing; biomarkers a identification in serum and plasma of patients and controls by simultaneous multi-analyte and metabolomic profiling.
Read the detailed description
Context :
Listeriosis is a rare, severe foodborne infection caused by the bacterium Listeria monocytogenes (Lm). It manifests as septicemia, central nervous system (CNS) infection and maternal-fetal (MF) infection. Its associated overall mortality is very high, above of 30%. A better knowledge on the factors involved in its occurrence and in clinical manifestations is therefore needed to improve outcome. Surveillance of human listeriosis in France relies on the mandatory reporting of cases and the submission of the corresponding Lm strains to the National Reference Centre for Listeria (NRCL).
A number of acquired risk factors for listeriosis have been identified, such as pregnancy, age, cirrhosis, renal insufficiency, diabetes, cancer, HIV infection, transplantation and immunosuppressive therapies. If listeriosis is rare, the exposure to Lm is universal. The high prevalence of known risk factors in the general population and the low occurrence of the disease suggest that unknown parameters, such as host genetic factors, contribute to the susceptibility to listeriosis. This is supported by animal studies, which have shown that genes involved in innate and cell-based immunity are critical to control listeriosis. However, no genetic study on host susceptibility to listeriosis in humans has been performed so far, in the absence of prospective collection of patients' samples.
Listeriosis diagnosis is based on Lm culture from clinical samples. This specific method lacks sensitivity, and the usefulness of PCR or serological assays have not been assessed in prospective case-control studies. Biomarkers are useful tools to diagnose infections and assess their severity, but their contribution to listeriosis diagnosis and prognosis has not been evaluated.
The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA), a national case-control prospective study on listeriosis, was launched in 2009. It enrolls all culture-proven cases declared to the NRCL: clinical and biological data and biological samples (plasma, serum, PBMC) are collected at inclusion for each patient. Controls with comparable background and presentation are also included. 818 cases have been included (427 S, 252 CNS and 107 MN) over 3.5 years, along with 456 controls.
Hypothesis :
- host genetic variation plays an important role in determining susceptibility to listeriosis and its clinical manifestations. Common host genetic variation in the human population may play a role in susceptibility in association with known acquired risk factors. Rare variants may also explain severe manifestations of listeriosis, such as death, severe persistent neurological impairment and fetal loss, in the absence of risk factors.
- biomarker patterns can assess and predict infection and infection severity. Immune responses may be tracked as a biological signature of invasive listeriosis
- biomarkers patterns could hopefully correlate with genotypic characterization as a phenotypic reflection of a genetically inadequate / missing link hampering the proper coordination of the immune response to Lm.
Methods :
- SNP arrays genotyping of the whole cohort
- Whole-exome sequencing of the whole cohort to identify rare variants
- Biomarkers identification in serum and plasma of patients and controls by simultaneous multi-analyte and metabolomic profiling:
The cohort is already constituted.
Expected results :
Better understanding of major biomedical aspects of listeriosis, namely host genetic susceptibility factors and diagnostic/prognostic biomarkers.
- Conditions
- Listeriosis
- Medical subject headings
- Listeriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Case patients | Patients with culture-proven listeriosis. Case patients are classified in 3 groups : * Septicemic infections: isolation of Lm in blood cultures. * CNS infections: isolation of Lm in cerebrospinal fluid, or brain stereotaxic biopsy, or by isolation of Lm in the blood with concomitant meningitis, or radiological encephalitis, rhombencephalitis, brain abscess or meningitis. * MF infections: defined by isolation of Lm in any maternal/fetal/neonatal bacteriological sample. All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses will be included in the MONALISA GENBIO study. | |
| Control patients | Patients without listeriosis but compatible clinical presentation. Control patients are divided in 3 groups. * Septicemic controls: febrile patient with same co-morbidities as septicemic cases. * CNS controls: patient with any neurological symptom leading to the empiric prescription of amoxicillin at meningeal dosage because of listeriosis presumption. * MF controls: febrile pregnant patient without obvious focal infection. All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses will be included in the MONALISA GENBIO study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection
Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection by whole exome sequencing and whole genome genotyping for all MONALISA cases and controls
Measured: 3 years
Secondary outcomes (2)
Biomarkers identification in serum and plasma of patients and controls
Biomarkers identification in serum and plasma of patients and controls by simultaneous multi-analyte and metabolomic profiling:
-Characterisation of a biological signature of listeriosis as a whole and for each form of infection.
Measured: 3 years
Biomarkers identification in serum and plasma of patients and controls
Biomarkers identification in serum and plasma of patients and controls by simultaneous multi-analyte and metabolomic profiling:
-Characterisation of the severity of infection (prognosis): death, fetal loss, neurological persisting impairment.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2016 (estimated)
- Study start16 Feb 2017
- Primary completion30 Sep 2021
- Study completion30 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ListeriosisStudies of the same condition, open and under way.
- More trials run by Institut PasteurThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 1,080 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Pasteur
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Icahn School of Medicine at Mount Sinai
- Responsible party
- Sponsor
- Investigators
- Marc Lecuit, Study director, Institut Pasteur
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02924220
- Sponsor's protocol ID
- 2016-038
- Other IDs
- ID-RCB number : 2016-A00650-51
- Acronym
- MONALISAGENBIO
- Status last verified
- Oct 2021
- First submitted
- 3 Oct 2016
- Last updated
- 18 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Susceptibility and Biomarkers in Listeriosis (MONALISA-GENBIO)
- ClinicalTrials.gov ID
- NCT02924220
- Acronym / sponsor ID
- MONALISAGENBIO / 2016-038
- Conditions
- Listeriosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,080 participants (actual)
- Lead sponsor
- Institut PasteurIndustry (pharma, biotech, devices)
- Collaborators
- Icahn School of Medicine at Mount Sinai
- Study start
- 16 Feb 2017 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 5 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Listeriosis is a rare, severe foodborne infection caused by the bacterium Listeria monocytogenes (Lm). It manifests as septicemia, central nervous system (CNS) infection and maternal-fetal (MF) infection. Its associated overall mortality is very high, above of 30%. A better knowledge on the factors involved in its occurrence and in clinical manifestations is therefore needed to improve outcome.
A number of frequent acquired risk factors for listeriosis have been identified, such as pregnancy, diabetes, cancer, HIV infection, and immunosuppressive therapies. However, no genetic study on host susceptibility to listeriosis in humans has been performed so far, in the absence of prospective collection of patients' samples. Also, listeriosis diagnosis is based on Lm culture from clinical samples. This method lacks sensitivity, and the contribution of biomarkers to listeriosis diagnosis and prognosis has not been evaluated.
The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA), is the first national case-control prospective study on listeriosis. It is implemented since 2009 and enrolls all culture-proven cases declared to the NRCL: and collects for each patient clinical and biological data and biological samples. Controls with comparable background and presentation are also included. 818 cases have been included (427 S, 252 CNS and 107 MN) over 3.5 years, along with 456 controls.
The aim of the study is to identify human genetic susceptibility factors to listeriosis, biomarkers to improve its diagnosis and prognosis (survival or death), and thereby help improve management of patients with listeriosis.
Samples from the completed cohort will be analyzed : SNPs genotyping and exam sequencing; biomarkers a identification in serum and plasma of patients and controls by simultaneous multi-analyte and metabolomic profiling.
Detailed description
Context :
Listeriosis is a rare, severe foodborne infection caused by the bacterium Listeria monocytogenes (Lm). It manifests as septicemia, central nervous system (CNS) infection and maternal-fetal (MF) infection. Its associated overall mortality is very high, above of 30%. A better knowledge on the factors involved in its occurrence and in clinical manifestations is therefore needed to improve outcome. Surveillance of human listeriosis in France relies on the mandatory reporting of cases and the submission of the corresponding Lm strains to the National Reference Centre for Listeria (NRCL).
A number of acquired risk factors for listeriosis have been identified, such as pregnancy, age, cirrhosis, renal insufficiency, diabetes, cancer, HIV infection, transplantation and immunosuppressive therapies. If listeriosis is rare, the exposure to Lm is universal. The high prevalence of known risk factors in the general population and the low occurrence of the disease suggest that unknown parameters, such as host genetic factors, contribute to the susceptibility to listeriosis. This is supported by animal studies, which have shown that genes involved in innate and cell-based immunity are critical to control listeriosis. However, no genetic study on host susceptibility to listeriosis in humans has been performed so far, in the absence of prospective collection of patients' samples.
Listeriosis diagnosis is based on Lm culture from clinical samples. This specific method lacks sensitivity, and the usefulness of PCR or serological assays have not been assessed in prospective case-control studies. Biomarkers are useful tools to diagnose infections and assess their severity, but their contribution to listeriosis diagnosis and prognosis has not been evaluated.
The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA), a national case-control prospective study on listeriosis, was launched in 2009. It enrolls all culture-proven cases declared to the NRCL: clinical and biological data and biological samples (plasma, serum, PBMC) are collected at inclusion for each patient. Controls with comparable background and presentation are also included. 818 cases have been included (427 S, 252 CNS and 107 MN) over 3.5 years, along with 456 controls.
Hypothesis :
- host genetic variation plays an important role in determining susceptibility to listeriosis and its clinical manifestations. Common host genetic variation in the human population may play a role in susceptibility in association with known acquired risk factors. Rare variants may also explain severe manifestations of listeriosis, such as death, severe persistent neurological impairment and fetal loss, in the absence of risk factors.
- biomarker patterns can assess and predict infection and infection severity. Immune responses may be tracked as a biological signature of invasive listeriosis
- biomarkers patterns could hopefully correlate with genotypic characterization as a phenotypic reflection of a genetically inadequate / missing link hampering the proper coordination of the immune response to Lm.
Methods :
- SNP arrays genotyping of the whole cohort
- Whole-exome sequencing of the whole cohort to identify rare variants
- Biomarkers identification in serum and plasma of patients and controls by simultaneous multi-analyte and metabolomic profiling:
The cohort is already constituted.
Expected results :
Better understanding of major biomedical aspects of listeriosis, namely host genetic susceptibility factors and diagnostic/prognostic biomarkers.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Case patients | – | –Patients with culture-proven listeriosis. Case patients are classified in 3 groups : * Septicemic infections: isolation of Lm in blood cultures. * CNS infections: isolation of Lm in cerebrospinal fluid, or brain stereotaxic biopsy, or by isolation of Lm in the blood with concomitant meningitis, or radiological encephalitis, rhombencephalitis, brain abscess or meningitis. * MF infections: defined by isolation of Lm in any maternal/fetal/neonatal bacteriological sample. All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses will be included in the MONALISA GENBIO study. |
| Control patients | – | –Patients without listeriosis but compatible clinical presentation. Control patients are divided in 3 groups. * Septicemic controls: febrile patient with same co-morbidities as septicemic cases. * CNS controls: patient with any neurological symptom leading to the empiric prescription of amoxicillin at meningeal dosage because of listeriosis presumption. * MF controls: febrile pregnant patient without obvious focal infection. All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses will be included in the MONALISA GENBIO study. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All patients already recruited in the MONALISA study will be included. The MONALISA study is the first prospective case-control study focused on invasive listeriosis. Cases are patients with culture-proven listeriosis. Controls are patients without listeriosis but compatible clinical presentation.
Key inclusion criteria (1 listed)
- All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses.
Key exclusion criteria (1 listed)
- Patients included in the MONALISA cohort without biological sample available.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection
Time frame: 3 years
Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection by whole exome sequencing and whole genome genotyping for all MONALISA cases and controls
2 secondary outcomes
Biomarkers identification in serum and plasma of patients and controls
Time frame: 3 years
Biomarkers identification in serum and plasma of patients and controls
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2021.
- Individual participant dataSharing planned: No
Related trials for Listeriosis
Recruiting
Genetic Susceptibility to Listeriosis
Listeriosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Lecuit study director
Institut Pasteur
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Listeriosis, run by Institut Pasteur at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2021; AzTrials last refreshed its copy on 8 Nov 2026.