Milieu Intérieur Collection - Genetic & Environmental Determinants Of Immune Phenotype Variance

NCT03905993 | Completed

• 3 other identifiers: 2017-070ID-RCB : 2018-A00861-5410-LABX-0069
• Study Type: observational
• Target: 956
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the determinants of immunologic variance within the general healthy population.

Conditions

Individuality; Healthy Subjects

Keywords

Immune response; Immune System; genotype-to-phenotype association; genetic variability; reference-based population

Outcome Measures

Primary Outcomes (1)

• Identify genetic associations with immune response variability

  Genome wide associations studies that combine whole genome genotyping data sets with immune response phenotypes to identify genetic regulators of immune function. These studies will be later completed with data from whole genome sequencing for more detailed genetic analysis.

  2024

Secondary Outcomes (1)

• Identify environmental associations with immune response variability

  2026

Study Arms (1)

Experimental: unique group.

At V0: 1238 subjects were screened At V1: 1012 subjects (12 later withdrew) gave the following samples: blood, nasal swab,stool. 323 subjects among 1000 gave one additional sample (Skin Biopsy) At V2: 504 subjects came at V2 to perform blood, nasal swab and stool samples

Eligibility Criteria

• Age: 20 Years - 69 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy adults subjects, aged from 20 to 69 years old, and whose ancestry for three generations was of Metropolitan French origin

You may qualify if:

• Subjects considered as healthy by the investigator based on medical history, clinical examination, laboratory results and ECG (blood sampling for laboratory assessments and ECG were performed at V0 and only after signed informed consent).
• Subjects who, according to the investigator, complied with the requirements of the protocol and were available for all scheduled visits at the investigational site.
• Healthy male or female aged between 20 and 69 (included) years
• Metropolitan French origin for 3 generations
• ≤BMI ≤ 32 kg/m²
• Ability to give their informed consent in writing
• Understanding of spoken and written French
• Affiliated to the French social security or assimilated regimens

You may not qualify if:

• Participation in another clinical study in the previous 3 months in which the subject had been exposed to an investigational product (pharmaceutical product or placebo or medical device) or concurrent participation in another clinical study during the study period
• Relatedness to previously recruited individuals in the study cohort
• Travel in (sub-)tropical countries within the previous 3 months
• For women: pregnant or breastfeeding or intending to become pregnant or peri-menopausal\*
• \* Peri-menopausal women as defined by menstrual irregularity: either a change in the menstrual cycle length of more than seven days (early perimenopause) or two or more missed periods with an interval of 60 days or more between periods (late perimenopause) (Stages of Reproductive Aging Workshop, STRAW)
• Any physical exercise within the previous 8 hours before study visits.
• Subjects following a special diet for medical reasons as prescribed by a GP or dietician (e.g. calorie restricted or weight-loss diet for significant overweight, cholesterol lowering diet or subjects suffering from any clinically diagnosed food allergy or intolerance)
• Alcohol abuse (more than 50 g of pure ethanol per day: for example, more than 4 x 150 mL glasses of wine, more than 4 x 250 mL glasses of beer, more than 4 x 40 mL glasses of high alcohol content drinks)
• Presence of evidence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to participate in the study satisfactorily.
• Severe/chronic/recurrent pathological conditions, among them:
• Past or present diagnosed cancer, lymphoma, leukemia to the exception of:
• Persons with a history of cancer who are disease-free without treatment for 5 years or more
• Women who are disease free for 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen
• Cutaneous or cervical basal cell carcinoma 10.2. Personal history of organ transplant 10.3. Congenital or acquired immune deficiency (any confirmed or suspected immunosuppressive or immunodeficient condition, including history of HIV infection) 10.4. Personal history of auto-immune diseases requiring or having previously required treatment (e.g. Rheumatoid Arthritis, Systemic Lupus Erythematosus, Sarcoidosis, Ankylosing Spondylitis, Autoimmune Hemolytic Anemia, Autoimmune Thrombocytopenic Purpura, Crohn's Disease, Psoriasis, Scleroderma, Wegener's Granulomatosis,Type I Diabetes, Thyroiditis,….) 10.5. Splenectomy 10.6. Acute or chronic, clinically significant, as determined by the investigator, pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests 10.7. History of clinically significant, as determined by the investigator, neurological disorder or seizures 10.8. Infectious diseases:
• Chronic infection (e.g. HIV, HBV, HCV…) or current acute infection or past acute infection based on investigator's judgment within the previous 3 months,

Sponsors & Collaborators

• Institut Pasteur: lead
• National Research Agency, France: collaborator

Related Publications (4)

• Patin E, Hasan M, Bergstedt J, Rouilly V, Libri V, Urrutia A, Alanio C, Scepanovic P, Hammer C, Jonsson F, Beitz B, Quach H, Lim YW, Hunkapiller J, Zepeda M, Green C, Piasecka B, Leloup C, Rogge L, Huetz F, Peguillet I, Lantz O, Fontes M, Di Santo JP, Thomas S, Fellay J, Duffy D, Quintana-Murci L, Albert ML; Milieu Interieur Consortium. Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors. Nat Immunol. 2018 Mar;19(3):302-314. doi: 10.1038/s41590-018-0049-7. Epub 2018 Feb 23.

  PMID: 29476184 BACKGROUND

• Piasecka B, Duffy D, Urrutia A, Quach H, Patin E, Posseme C, Bergstedt J, Charbit B, Rouilly V, MacPherson CR, Hasan M, Albaud B, Gentien D, Fellay J, Albert ML, Quintana-Murci L; Milieu Interieur Consortium. Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges. Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E488-E497. doi: 10.1073/pnas.1714765115. Epub 2017 Dec 27.

  PMID: 29282317 BACKGROUND

• Thomas S, Rouilly V, Patin E, Alanio C, Dubois A, Delval C, Marquier LG, Fauchoux N, Sayegrih S, Vray M, Duffy D, Quintana-Murci L, Albert ML; Milieu Interieur Consortium. The Milieu Interieur study - an integrative approach for study of human immunological variance. Clin Immunol. 2015 Apr;157(2):277-93. doi: 10.1016/j.clim.2014.12.004. Epub 2015 Jan 3.

  PMID: 25562703 BACKGROUND

• Clave E, Araujo IL, Alanio C, Patin E, Bergstedt J, Urrutia A, Lopez-Lastra S, Li Y, Charbit B, MacPherson CR, Hasan M, Melo-Lima BL, Douay C, Saut N, Germain M, Tregouet DA, Morange PE, Fontes M, Duffy D, Di Santo JP, Quintana-Murci L, Albert ML, Toubert A; Milieu Interieur Consortium. Human thymopoiesis is influenced by a common genetic variant within the TCRA-TCRD locus. Sci Transl Med. 2018 Sep 5;10(457):eaao2966. doi: 10.1126/scitranslmed.aao2966.

  PMID: 30185651 BACKGROUND

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

1. DNA extracted from whole blood 2. Whole blood stimulations for 40 TruCulture stimulation conditions from which there are * Trizol stabilized cell pellets and/or extracted RNA * Culture supernatants in aliquots 3. Fecal samples and extracted DNA 4. Nasal swab samples, extracted DNA and liquid supernatant 5. Plasma from whole blood 6. Frozen PBMCs 7. Fibroblast cell lines (322 donors) and derived iPSCs (4 donors) 8. EBV cell lines (203 donors)

Study Officials

• Lluis Quintana-Murci, PhD

  Institut Pasteur

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: April 8, 2019
• Study Start: September 17, 2012
• Primary Completion: August 8, 2013
• Study Completion: August 8, 2013
• Last Updated: May 20, 2022

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR, ANALYTIC CODE
• Time Frame: Until April 2028
• Access Criteria: All IPD that underlie results in peer reviewed publications may be shared for scientific collaborations following a request and review by the Milieu Interieur data and sample access committee.