Term and Preterm Neonates (24-41 Weeks Gestational Age)NEOMAITNCT02403089
Ontogeny of MAIT Cells in Neonates and Hematopoietic Stem Cell Transplant Recipients
An observational study of Term and Preterm Neonates (24-41 Weeks Gestational Age) and Hematopoietic Stem Cell Transplant Recipient Children, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The objective of this study is 1/ to determine the rate and kinetics of MAIT cell expansion and maturation in neonates in relation with gestational age, and in HSCT recipient children in relation with the source of donor stem cells, 2/ to correlate gut microbiota diversity and function with MAIT cell maturation and… Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Term and Preterm Neonates (24-41 Weeks Gestational Age), Hematopoietic Stem Cell Transplant Recipient Children
- What is being tested?
- Tubes fund recovery blood count and the rest of the blood test and stool sample
- How many people
- 300 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2015to Feb 2018
- 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 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: newborns hospitalized in the Neonatal Intensive Care Unit of the Hospital Robert Debré and grafted children hospitalized in the Hematology-Immunology Pediatric Service of the Hospital Robert Debré
Who may be able to join
- neonates 24-41 weeks gestational age
- hematopoietic stem cell transplant recipient children (< 18 years old, donor source: cord blood or genoidentical donor)
Who cannot join
- neonates : chromosomal abnormalities detected before birth
- source of HSCT: phenol-identical donors
Trial locations and contacts
1 site in 1 country.
About this study
The objective of this study is 1/ to determine the rate and kinetics of MAIT cell expansion and maturation in neonates in relation with gestational age, and in HSCT recipient children in relation with the source of donor stem cells, 2/ to correlate gut microbiota diversity and function with MAIT cell maturation and function in neonates and HSCT recipients; and 3/ to link MAIT cells and gut microbiota composition with microbial infections and severe intestinal inflammatory events in term and preterm neonates, and in HSCT recipients
Read the detailed description
The mucosa-associated invariant T (MAIT) cells are innate-like T cells with restricted T cell receptor (TCR) usage, which are preferentially localized in mucosal tissues and respond to microbial infection by rapidly producing cytokines and cytotoxic effectors. They recognize the non-classical related molecule (MR1). MAIT cells react against a newly identified class of antigens presented by MR1: Riboflavin (Rib) precursors, which are found in most bacteria and yeasts. Currently, very little is known about the ontogeny of MAIT cells in the human, because of the difficulty to follow longitudinally their development. Cross-sectional studies have identified only the initial (cord blood) and final (adult subjects) steps of human MAIT cell maturation program. Moreover, there are no data on relationships between human MAIT cell expansion and maturation, and gut microbiota development. Given the potential importance of MAIT cells in protection from microbial infections at epithelial surfaces, we will investigate the maturation dynamics of MAIT cells in relation with gut microbiota diversity and function in two clinical settings characterized by a high predisposition to severe microbial infections before the establishment of protective adaptive immunity, namely i/ the neonatal period and ii/ the early immune reconstitution period following allogeneic hematopoietic stem cell transplantation (HSCT) in children. Our study will combine multiparametric phenotypic and functional characterization of MAIT cells with the use of new molecular microbiota analytic methodology (high throughput sequencing, metagenomics, Rib microbiology) to determine how the presence or functionality of MAIT cells is influenced by the gut microbiota.
Our consortium is composed of three independent research teams, experts in innate immunity, microbial ecology and MAIT cell biology, three independent clinical teams providing exceptional resources to patient samples, and one team providing expertise for methodology and statistical analysis. Their synergistic interaction will offer the various complementary expertise that is necessary for this project.
This project will decipher how MAIT cell numbers or functions are influenced by the gut microbiota composition, and reciprocally, how MAIT cells regulate or control expansion of gut microbiota components competing with opportunistic or pathogenic bacteria or responsible for infections. Ultimately, this study will determine how and when gut microbiota and MAIT cell interactions are involved in the control of severe infectious or intestinal inflammatory events in high risk infants, an indispensable step to design predictive biomarkers and ultimately propose new therapeutic options.
- Conditions
- Term and Preterm Neonates (24-41 Weeks Gestational Age), Hematopoietic Stem Cell Transplant Recipient Children
- Being tested
- Tubes fund recovery blood count, the rest of the blood test and stool sample
- Keywords
- MAIT (Mucosal-Associated Invariant T) cells, Gut microbiota, Preterm birth, Hematopoietic stem cell transplantation, Microbial infections
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tubes fund recovery blood countOther
Tubes fund recovery of blood counts among newborns
the rest of the blood test and stool sampleOther
blood samples on the recovery kinetics after transplant. The rest of the blood test and stool sample done as part of a routine examination.
| Study group | Role | What they receive |
|---|---|---|
| neonates | neonates 24-41 weeks gestational age Receives: Other: Tubes fund recovery blood count | |
| children | hematopoietic stem cell transplant recipient children (< 18 years old, donor source: cord blood or genoidentical donor) Receives: Other: the rest of the blood test and stool sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
MAIT cell numbering neonates after birth
Absolute number, percentage and phenotype of MAIT cells by flow cytometry in the circulating blood after birth according to gestational age and / or maternal-fetal infections (IMF), or after allogeneic HSCT according to the origin of HSCs.
Measured: to 60days
Secondary outcomes (2)
Absolute number of MAIT
Absolute number and percentage of MAIT among mothers of infants on the day of delivery and in geno-identical donors before transplantation.
Measured: to 60days
Absolute number of other immune cell populations
Absolute number and percentage of other immune cell populations by flow cytometry on the same blood samples.
Measured: to 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionFeb 2018
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Term and Preterm Neonates (24-41 Weeks Gestational Age)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Other
- Time perspective
- Prospective
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Institut Curie
- Responsible party
- Sponsor
- Investigators
- Biran Valérie, PHD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02403089
- Sponsor's protocol ID
- NI14006
- Acronym
- NEOMAIT
- Status last verified
- Feb 2018
- First submitted
- 6 Mar 2015
- Last updated
- 3 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Ben Youssef G, Tourret M, Salou M, Ghazarian L, Houdouin V, Mondot S, Mburu Y, Lambert M, Azarnoush S, Diana JS, Virlouvet AL, Peuchmaur M, Schmitz T, Dalle JH, Lantz O, Biran V, Caillat-Zucman S. Ontogeny of human mucosal-associated invariant T cells and related T cell subsets. J Exp Med. 2018 Feb 5;215(2):459-479. doi: 10.1084/jem.20171739. Epub 2018 Jan 16.
PubMed 29339446Tourret M, Talvard-Balland N, Lambert M, Ben Youssef G, Chevalier MF, Bohineust A, Yvorra T, Morin F, Azarnoush S, Lantz O, Dalle JH, Caillat-Zucman S. Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy. J Immunother Cancer. 2021 Oct;9(10):e003123. doi: 10.1136/jitc-2021-003123.
PubMed 34615705
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ontogeny of MAIT Cells in Neonates and Hematopoietic Stem Cell Transplant Recipients
- ClinicalTrials.gov ID
- NCT02403089
- Acronym / sponsor ID
- NEOMAIT / NI14006
- Conditions
- Term and Preterm Neonates (24-41 Weeks Gestational Age), Hematopoietic Stem Cell Transplant Recipient Children
- Keywords
- MAIT (Mucosal-Associated Invariant T) cells, Gut microbiota, Preterm birth, Hematopoietic stem cell transplantation, Microbial infections
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Institut Curie
- Study start
- Mar 2015 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 31 Mar 2015 (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.
The objective of this study is 1/ to determine the rate and kinetics of MAIT cell expansion and maturation in neonates in relation with gestational age, and in HSCT recipient children in relation with the source of donor stem cells, 2/ to correlate gut microbiota diversity and function with MAIT cell maturation and function in neonates and HSCT recipients; and 3/ to link MAIT cells and gut microbiota composition with microbial infections and severe intestinal inflammatory events in term and preterm neonates, and in HSCT recipients
Detailed description
The mucosa-associated invariant T (MAIT) cells are innate-like T cells with restricted T cell receptor (TCR) usage, which are preferentially localized in mucosal tissues and respond to microbial infection by rapidly producing cytokines and cytotoxic effectors. They recognize the non-classical related molecule (MR1). MAIT cells react against a newly identified class of antigens presented by MR1: Riboflavin (Rib) precursors, which are found in most bacteria and yeasts. Currently, very little is known about the ontogeny of MAIT cells in the human, because of the difficulty to follow longitudinally their development. Cross-sectional studies have identified only the initial (cord blood) and final (adult subjects) steps of human MAIT cell maturation program. Moreover, there are no data on relationships between human MAIT cell expansion and maturation, and gut microbiota development. Given the potential importance of MAIT cells in protection from microbial infections at epithelial surfaces, we will investigate the maturation dynamics of MAIT cells in relation with gut microbiota diversity and function in two clinical settings characterized by a high predisposition to severe microbial infections before the establishment of protective adaptive immunity, namely i/ the neonatal period and ii/ the early immune reconstitution period following allogeneic hematopoietic stem cell transplantation (HSCT) in children. Our study will combine multiparametric phenotypic and functional characterization of MAIT cells with the use of new molecular microbiota analytic methodology (high throughput sequencing, metagenomics, Rib microbiology) to determine how the presence or functionality of MAIT cells is influenced by the gut microbiota.
Our consortium is composed of three independent research teams, experts in innate immunity, microbial ecology and MAIT cell biology, three independent clinical teams providing exceptional resources to patient samples, and one team providing expertise for methodology and statistical analysis. Their synergistic interaction will offer the various complementary expertise that is necessary for this project.
This project will decipher how MAIT cell numbers or functions are influenced by the gut microbiota composition, and reciprocally, how MAIT cells regulate or control expansion of gut microbiota components competing with opportunistic or pathogenic bacteria or responsible for infections. Ultimately, this study will determine how and when gut microbiota and MAIT cell interactions are involved in the control of severe infectious or intestinal inflammatory events in high risk infants, an indispensable step to design predictive biomarkers and ultimately propose new therapeutic options.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| neonates | – | Other: Tubes fund recovery blood countneonates 24-41 weeks gestational age |
| children | – | Other: the rest of the blood test and stool samplehematopoietic stem cell transplant recipient children (< 18 years old, donor source: cord blood or genoidentical donor) |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- newborns hospitalized in the Neonatal Intensive Care Unit of the Hospital Robert Debré and grafted children hospitalized in the Hematology-Immunology Pediatric Service of the Hospital Robert Debré
Key inclusion criteria (2 listed)
- neonates 24-41 weeks gestational age
- hematopoietic stem cell transplant recipient children (< 18 years old, donor source: cord blood or genoidentical donor)
Key exclusion criteria (2 listed)
- neonates : chromosomal abnormalities detected before birth
- source of HSCT: phenol-identical donors
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 |
|---|---|---|
| Tubes fund recovery blood countTubes fund recovery of blood counts among newborns | Other | neonates |
| the rest of the blood test and stool sampleblood samples on the recovery kinetics after transplant. The rest of the blood test and stool sample done as part of a routine examination. | Other | children |
Primary outcome
MAIT cell numbering neonates after birth
Time frame: to 60days
Absolute number, percentage and phenotype of MAIT cells by flow cytometry in the circulating blood after birth according to gestational age and / or maternal-fetal infections (IMF), or after allogeneic HSCT according to the origin of HSCs.
2 secondary outcomes
Absolute number of MAIT
Time frame: to 60days
Absolute number of other immune cell populations
Time frame: to 60 days
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 3 Feb 2023.
- Results publication: PubMed 29339446Ben Youssef G, Tourret M, Salou M, Ghazarian L, Houdouin V, Mondot S, Mburu Y, Lambert M, Azarnoush S, Diana JS, Virlouvet AL, Peuchmaur M, Schmitz T, Dalle JH, Lantz O, Biran V, Caillat-Zucman S. Ontogeny of human mucosal-associated invariant T cells and related T cell subsets. J Exp Med. 2018 Feb 5;215(2):459-479. doi: 10.1084/jem.20171739. Epub 2018 Jan 16.
- Derived from this study: PubMed 34615705Tourret M, Talvard-Balland N, Lambert M, Ben Youssef G, Chevalier MF, Bohineust A, Yvorra T, Morin F, Azarnoush S, Lantz O, Dalle JH, Caillat-Zucman S. Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy. J Immunother Cancer. 2021 Oct;9(10):e003123. doi: 10.1136/jitc-2021-003123.
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.
Biran Valérie, PHD principal investigator
Assistance Publique - Hôpitaux de Paris
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 Term and Preterm Neonates (24-41 Weeks Gestational Age) and Hematopoietic Stem Cell Transplant Recipient Children, run by Assistance Publique - Hôpitaux de Paris 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 2 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: finished, as of the sponsor's last update on 3 Feb 2023. 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?
MAIT cell numbering neonates after birth (time frame: to 60days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02403089, which also lists 2 linked publications.
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 3 Feb 2023.