Infectious DiseasePREDISPOSITINCT06102070
Genetic Susceptibility to Severe Infections
An observational study of Infectious Disease, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial summary
Only a fraction of individuals infected with microbes develop clinical disease. This observation raises fundamental questions about the pathogenesis of infectious diseases. There is a complex interaction between environmental (microbial and non-microbial) and human (genetic and non-genetic) factors. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Infectious Disease
- What is being tested?
- Blood samples drawing and Skin biopsy
- How many people
- 2,000 participants
- Where
- 1 siteFrance
- Study dates
- 18 Feb 2022to 18 Oct 2038
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: 1. Patients (index cases) will be recruited on the basis of a proven diagnosis of severe infection, including in particular but not exhaustively severe viral, parasitic, fungal and/or bacterial infections, prospectively. 2. Relatives of the applicant: Father, Mother, Brother, Sister, Grandparents, Uncles, Aunts, Cousins, Nephews, Nieces
Who may be able to join
- to sign the informed consent signed by the patient. In the case of a minor patient, consent is signed by the holders of parental authority. In the case of a protected adult patient, the consent is signed by their legal representative. In the case of an adult patient unable to consent at the time of inclusion, consent is signed by a family member.
- to have a proven rare and severe infection
- to be hospitalized or followed in a specialized hospital department, in the emergency room or in intensive care
- to be affiliated to the French Social Security system
- for relatives, to be related to the index case up to the 3rd degree: Parents, Children, Brother, Sister, Grandparents, Uncles, Aunts, Cousins, Nephews, Nieces
Who cannot join
- to have an acquired immunodeficiency (having received immunosuppressive treatment in the 3 months preceding the onset of the disease or being HIV positive)
- pregnant woman at the time of illness
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Centre d'Etudes des Déficits Immunitaires (CEDI), Hôpital Necker-Enfants
Paris, Île-de-France Region, 75015
jacinta MD BUSTAMANTE, MD-PHD, 0171196004, jacinta.bustamante@aphp.fr
About this study
Official title: Genetic Susceptibility to Severe Infections Including in Particular But Not Exhaustively All Types of Viral, Bacterialn and Fungal Infections.
Only a fraction of individuals infected with microbes develop clinical disease. This observation raises fundamental questions about the pathogenesis of infectious diseases. There is a complex interaction between environmental (microbial and non-microbial) and human (genetic and non-genetic) factors. This will determine the quality of the immune response against the infectious agent and the clinical manifestation. By definition, individuals who die from an infection have defective immunity to the pathogen in question (immune agent (immune deficiency).
The investigation of individual variability in the development of infectious diseases began in the early 20th. The first evidence to support the hypothesis that individual variability variability and immune deficiencies were hereditary came from observations of familial cases or genetic isolates genetic isolates (from a homogeneous population) of rare or common infectious diseases, which in some cases Mendelian heredity hat predisposition to infectious diseases runs in families even more so than diseases associated with less determined environmental factors, such as certain cancers. such as certain cancers. Finally, studies comparing the rate of concordance of infectious diseases between monozygotic and dizygotic twins also implicate genetic factors in disease susceptibility.
Read more
These observations were validated by the discovery of genetic defects associated with severe infectious diseases, leading to proof of concept. While a number of hereditary immune deficiencies associated with susceptibility to multiple pathogens or microorganisms, a growing number of new and rare new and rare immune deficiencies conferring restricted susceptibility to infections caused by a single caused by a single pathogen family, or even a single pathogen, in otherwise healthy children, have recently been identified (one gene, one pathogen). As a result, a dozen Mendelian clinical syndromes characterized by restricted susceptibility are now known. Over the last 20 years, it has been proven that these "idiopathic" infections were immune deficiencies.
The investigators now wish to study new severe infections, including but not limited to viral, fungal and bacterial infections. viral, fungal, bacterial and parasitic infections. This should lead to a better understanding of the pathophysiology of each disease, the development of new therapeutics and better patient care.
Read the detailed description
Justification of the number of subjects:
The prevalence of the various severe infections we wish to explore ranges from one case in 50,000 to one case in 1,000,000 individuals; consequently, we plan to recruit only a small cohort of patients per pathology. Due to the exploratory nature of this research, no sample size calculation is possible.
ELIGIBILITY CRITERIA
Inclusion criteria :
- Index cases (patients)
- Informed consent signed by the patient. In the case of a minor patient, consent must be signed by the holders of parental authority. In the case of a protected adult patient, consent is signed by his or her signed by the patient's legal representative. In the case of an adult patient unable to consent at the time of consent is signed by a family member.
- have a proven rare and severe infection defined by at least one of the following elements:
- Acute, life-threatening infection requiring hospitalization, especially in an intensive particularly in intensive care.
- Recurrent and/or chronic infections requiring frequent hospitalization or follow-up visits hospitalization or follow-up visits (dermatology, cardiology, neurology, infectious diseases, immunology, etc.), infectious diseases, immunology, etc.).
- Acute and/or chronic infections leading to sequelae (motor or cognitive deficits, etc.).
- Disseminated infection by an opportunistic microbe.
- be hospitalized or followed in a specialized hospital ward, emergency room or intensive care unit
- be affiliated to a Social Security scheme.
- Related
- have informed consent signed by the adult relative. In the case of a minor relative, the consent is consent is signed by the holders of parental authority. In the case of an adult relative the consent is signed by his or her legal representative
- be related to the index case up to the 3rd degree: Parents, Children, Brother, Sister, Grandparents, Uncles, Aunts, Cousins, Nephews, Nieces
- be affiliated to a Social Security system
Non-inclusion criteria :
- Index case:4/4 C18-41 _Predisposition_Synopsis_V2.0_20220324
- Acquired immunodeficiency (having received immunosuppressive treatment in the 3 months prior to the onset of the disease or HIV-positive)
- Pregnant at the time of illness
- Person under court protection
- Related persons :
- Pregnant or breast-feeding woman
- Person under court protection
- Conditions
- Infectious Disease
- Being tested
- Blood samples drawing, Skin biopsy
- Medical subject headings
- Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samples drawingOther
10 ml of periferal blood
Skin biopsyOther
Skin biopsy only in some index cases depending of the pathology at the recruitment
| Study group | Role | What they receive |
|---|---|---|
| Predisposition | individuals suffering of having previously suffered of severe infectious diseases Receives: Other: Blood samples drawing; Other: Skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of chromosomal regions associated with the disease through a "homozygosity mapping" study on multiplex and/or consanguineous families.
Whole genome genotyping using high density microarrays (Affymetrix 6.0 type or equivalent) on the gDNA of the index case and its relatives. Exome data will also be used for homozygosity calculation.
Measured: through study completion, an average of 10 years
Identification of candidate genes for genetic susceptibility to infectious diseases
- To sequence using the high-throughput sequencing technique (exome or genome).
- To check the genetic segregation of mutations identified in relatives in each family.
Measured: through study completion, an average of 10 years
Validation of candidate genes as factor of susceptibility to infectious diseases
To validate the pathogenic effect of the mutation by functional and complementation tests on patient cells and control cells, and in an overexpression system
Measured: through study completion, an average of 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2023
- Study start18 Feb 2022
- Primary completion17 Feb 2037 (estimated)
- Study completion18 Oct 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infectious DiseaseStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06102070
- Sponsor's protocol ID
- C18-41
- Acronym
- PREDISPOSITI
- Status last verified
- Jul 2026
- First submitted
- 29 Sep 2023
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Susceptibility to Severe Infections Including in Particular But Not Exhaustively All Types of Viral, Bacterialn and Fungal Infections.
- ClinicalTrials.gov ID
- NCT06102070
- Acronym / sponsor ID
- PREDISPOSITI / C18-41
- Conditions
- Infectious Disease
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- 18 Feb 2022 (actual)
- Primary completion
- 17 Feb 2037 (estimated)
- Study completion
- 18 Oct 2038 (estimated)
- First posted
- 26 Oct 2023 (actual)
- 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.
Only a fraction of individuals infected with microbes develop clinical disease. This observation raises fundamental questions about the pathogenesis of infectious diseases. There is a complex interaction between environmental (microbial and non-microbial) and human (genetic and non-genetic) factors. This will determine the quality of the immune response against the infectious agent and the clinical manifestation. By definition, individuals who die from an infection have defective immunity to the pathogen in question (immune agent (immune deficiency).
The investigation of individual variability in the development of infectious diseases began in the early 20th. The first evidence to support the hypothesis that individual variability variability and immune deficiencies were hereditary came from observations of familial cases or genetic isolates genetic isolates (from a homogeneous population) of rare or common infectious diseases, which in some cases Mendelian heredity hat predisposition to infectious diseases runs in families even more so than diseases associated with less determined environmental factors, such as certain cancers. such as certain cancers. Finally, studies comparing the rate of concordance of infectious diseases between monozygotic and dizygotic twins also implicate genetic factors in disease susceptibility.
These observations were validated by the discovery of genetic defects associated with severe infectious diseases, leading to proof of concept. While a number of hereditary immune deficiencies associated with susceptibility to multiple pathogens or microorganisms, a growing number of new and rare new and rare immune deficiencies conferring restricted susceptibility to infections caused by a single caused by a single pathogen family, or even a single pathogen, in otherwise healthy children, have recently been identified (one gene, one pathogen). As a result, a dozen Mendelian clinical syndromes characterized by restricted susceptibility are now known. Over the last 20 years, it has been proven that these "idiopathic" infections were immune deficiencies.
The investigators now wish to study new severe infections, including but not limited to viral, fungal and bacterial infections. viral, fungal, bacterial and parasitic infections. This should lead to a better understanding of the pathophysiology of each disease, the development of new therapeutics and better patient care.
Detailed description
Justification of the number of subjects:
The prevalence of the various severe infections we wish to explore ranges from one case in 50,000 to one case in 1,000,000 individuals; consequently, we plan to recruit only a small cohort of patients per pathology. Due to the exploratory nature of this research, no sample size calculation is possible.
ELIGIBILITY CRITERIA
Inclusion criteria :
- Index cases (patients)
- Informed consent signed by the patient. In the case of a minor patient, consent must be signed by the holders of parental authority. In the case of a protected adult patient, consent is signed by his or her signed by the patient's legal representative. In the case of an adult patient unable to consent at the time of consent is signed by a family member.
- have a proven rare and severe infection defined by at least one of the following elements:
- Acute, life-threatening infection requiring hospitalization, especially in an intensive particularly in intensive care.
- Recurrent and/or chronic infections requiring frequent hospitalization or follow-up visits hospitalization or follow-up visits (dermatology, cardiology, neurology, infectious diseases, immunology, etc.), infectious diseases, immunology, etc.).
- Acute and/or chronic infections leading to sequelae (motor or cognitive deficits, etc.).
- Disseminated infection by an opportunistic microbe.
- be hospitalized or followed in a specialized hospital ward, emergency room or intensive care unit
- be affiliated to a Social Security scheme.
- Related
- have informed consent signed by the adult relative. In the case of a minor relative, the consent is consent is signed by the holders of parental authority. In the case of an adult relative the consent is signed by his or her legal representative
- be related to the index case up to the 3rd degree: Parents, Children, Brother, Sister, Grandparents, Uncles, Aunts, Cousins, Nephews, Nieces
- be affiliated to a Social Security system
Non-inclusion criteria :
- Index case:4/4 C18-41 _Predisposition_Synopsis_V2.0_20220324
- Acquired immunodeficiency (having received immunosuppressive treatment in the 3 months prior to the onset of the disease or HIV-positive)
- Pregnant at the time of illness
- Person under court protection
- Related persons :
- Pregnant or breast-feeding woman
- Person under court protection
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Predisposition | – | Other: Blood samples drawing, Other: Skin biopsyindividuals suffering of having previously suffered of severe infectious diseases |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 1. Patients (index cases) will be recruited on the basis of a proven diagnosis of severe infection, including in particular but not exhaustively severe viral, parasitic, fungal and/or bacterial infections, prospectively. 2. Relatives of the applicant: Father, Mother, Brother, Sister, Grandparents, Uncles, Aunts, Cousins, Nephews, Nieces
Key inclusion criteria (5 listed)
- to sign the informed consent signed by the patient. In the case of a minor patient, consent is signed by the holders of parental authority. In the case of a protected adult patient, the consent is signed by their legal representative. In the case of an adult patient unable to consent at the time of inclusion, consent is signed by a family member.
- to have a proven rare and severe infection
- to be hospitalized or followed in a specialized hospital department, in the emergency room or in intensive care
- to be affiliated to the French Social Security system
- for relatives, to be related to the index case up to the 3rd degree: Parents, Children, Brother, Sister, Grandparents, Uncles, Aunts, Cousins, Nephews, Nieces
Key exclusion criteria (2 listed)
- to have an acquired immunodeficiency (having received immunosuppressive treatment in the 3 months preceding the onset of the disease or being HIV positive)
- pregnant woman at the time of illness
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samples drawing10 ml of periferal blood | Other | Predisposition |
| Skin biopsySkin biopsy only in some index cases depending of the pathology at the recruitment | Other | Predisposition |
Primary outcome
Identification of chromosomal regions associated with the disease through a "homozygosity mapping" study on multiplex and/or consanguineous families.
Time frame: through study completion, an average of 10 years
Whole genome genotyping using high density microarrays (Affymetrix 6.0 type or equivalent) on the gDNA of the index case and its relatives. Exome data will also be used for homozygosity calculation.
Identification of candidate genes for genetic susceptibility to infectious diseases
Time frame: through study completion, an average of 10 years
1. To sequence using the high-throughput sequencing technique (exome or genome). 2. To check the genetic segregation of mutations identified in relatives in each family.
Validation of candidate genes as factor of susceptibility to infectious diseases
Time frame: through study completion, an average of 10 years
To validate the pathogenic effect of the mutation by functional and complementation tests on patient cells and control cells, and in an overexpression system
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
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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.
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 Infectious Disease, run by Institut National de la Santé Et de la Recherche Médicale, France 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 5 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 7 Jul 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jacinta Md BUSTAMANTE, MD-PhD (01 71 19 60 04, jacinta.bustamante@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of chromosomal regions associated with the disease through a "homozygosity mapping" study on multiplex and/or consanguineous families. (time frame: through study completion, an average of 10 years). The study lists 3 primary outcomes in all. 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 7 Jul 2026.