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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04880720
Other study ID # RECHMPL20_0454
Secondary ID
Status Completed
Phase
First received
Last updated
Start date July 19, 2021
Est. completion date November 16, 2022

Study information

Verified date January 2023
Source University Hospital, Montpellier
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Immune aging or immunosenescence is characterized by a loss of T cell clonal diversity and a contraction of naïve T cells with proliferative capacity associated with the functional impairment of many others immune cells as well as a chronic low degree of inflammation. A restrictive T cell repertoire is likely more prone to antigen-mediated exhaustion observed during chronic viral infections. Notably, lymphopenia is the most consistent laboratory abnormality in COVID-19 infected patients and both lung-resident and circulating T cells potently up-regulate markers of T cell exhaustion. It is not clear today if the association of COVID-19 disease severity with age is mainly related with the immunosenescence of infected patients. Interestingly, T cell exhaustion and premature immunosenescence have also been observed in chronic inflammatory diseases such as rheumatoid arthritis (RA). To better understand the immunological mechanisms involved in SARS-Cov-2 pathophysiology, the investigators propose to compare the immunosenescence patterns observed during RA, aging and SARS-Cov-2 infected patients in order to design improved therapeutic interventions.


Recruitment information / eligibility

Status Completed
Enrollment 43
Est. completion date November 16, 2022
Est. primary completion date May 16, 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria for Active RA Patients: - Patients with rheumatoid arthritis (RA) meeting the 2010 ACR/EULAR diagnostic criteria - Patients in inflammatory flare of RA (DAS28 > 3.2) - Patients who have been off biological disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic antirheumatic drugs (tsDMARDs) for RA for at least 2 weeks (except for rituximab, where a delay of at least 12 months is required) - Conventional synthetic DMARDs (Methotrexate, Hydroxychloroquine, Leflunomide, Sulfasalazine) are allowed - Beneficiary of a social security system - Informed consent Inclusion Criteria for Healthy Controls: - Absence of chronic diseases and current infection - Beneficiary of a social security system - Informed consent Inclusion Criteria for COVID-19+ Patients: - Patients with ongoing SARS-Cov-2 infection (PCR+) - Patients hospitalized at D7-D14 of symptoms onset - Patients with two or more SARS-Cov-2 symptoms (including fever, cough, dyspnea, sore throat, chest pain, anosmia, diarrhea) - Membership in or beneficiary of a social security scheme - Collection of free and informed consent Exclusion Criteria for All Groups: - Subjects under 18 years of age - HIV positive patients - Diabetic patients - Morbidly obese patients (BMI > 40kg/m2) - Use of senolytic drugs in the week prior to inclusion (azithromycin, metformin, cyclosporine, JAK inhibitors) - Use of steroids in doses greater than 10 mg/day in the week prior to inclusion - Subjects unable to give consent - Pregnant, breastfeeding, or non-menopausal women not taking effective contraception - Vulnerable subjects protected by law - Subjects under guardianship or curatorship

Study Design


Intervention

Other:
Blood sampling
Blood sampling - 10mL

Locations

Country Name City State
France CHU Montpellier Montpellier

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

References & Publications (25)

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Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010 Oct;11(10):889-96. doi: 10.1038/ni.1937. Epub 2010 Sep 20. — View Citation

Bowers NL, Helton ES, Huijbregts RP, Goepfert PA, Heath SL, Hel Z. Immune suppression by neutrophils in HIV-1 infection: role of PD-L1/PD-1 pathway. PLoS Pathog. 2014 Mar 13;10(3):e1003993. doi: 10.1371/journal.ppat.1003993. eCollection 2014 Mar. — View Citation

Campos C, Pera A, Sanchez-Correa B, Alonso C, Lopez-Fernandez I, Morgado S, Tarazona R, Solana R. Effect of age and CMV on NK cell subpopulations. Exp Gerontol. 2014 Jun;54:130-7. doi: 10.1016/j.exger.2014.01.008. Epub 2014 Jan 17. — View Citation

Cloke T, Munder M, Bergin P, Herath S, Modolell M, Taylor G, Muller I, Kropf P. Phenotypic alteration of neutrophils in the blood of HIV seropositive patients. PLoS One. 2013 Sep 9;8(9):e72034. doi: 10.1371/journal.pone.0072034. eCollection 2013. — View Citation

D'Antiga L. Coronaviruses and Immunosuppressed Patients: The Facts During the Third Epidemic. Liver Transpl. 2020 Jun;26(6):832-834. doi: 10.1002/lt.25756. Epub 2020 Apr 24. No abstract available. — View Citation

de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34. doi: 10.1038/nrmicro.2016.81. Epub 2016 Jun 27. — View Citation

Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA, Witkowski JM, Franceschi C. Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes? Front Immunol. 2018 Jan 10;8:1960. doi: 10.3389/fimmu.2017.01960. eCollection 2017. — View Citation

Giacalone VD, Margaroli C, Mall MA, Tirouvanziam R. Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease. Int J Mol Sci. 2020 Jan 28;21(3):851. doi: 10.3390/ijms21030851. — View Citation

Goronzy JJ, Lee WW, Weyand CM. Aging and T-cell diversity. Exp Gerontol. 2007 May;42(5):400-6. doi: 10.1016/j.exger.2006.11.016. Epub 2007 Jan 10. — View Citation

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;: — View Citation

Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020 Apr;10(2):102-108. doi: 10.1016/j.jpha.2020.03.001. Epub 2020 Mar 5. — View Citation

Li X, Xu S, Yu M, Wang K, Tao Y, Zhou Y, Shi J, Zhou M, Wu B, Yang Z, Zhang C, Yue J, Zhang Z, Renz H, Liu X, Xie J, Xie M, Zhao J. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol. 2020 Jul;146(1):110-118. doi: 10.1016/j.jaci.2020.04.006. Epub 2020 Apr 12. — View Citation

Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020 Dec;9(1):727-732. doi: 10.1080/22221751.2020.1746199. — View Citation

Maringer K, Fernandez-Sesma A. Message in a bottle: lessons learned from antagonism of STING signalling during RNA virus infection. Cytokine Growth Factor Rev. 2014 Dec;25(6):669-79. doi: 10.1016/j.cytogfr.2014.08.004. Epub 2014 Aug 24. — View Citation

Nicolas-Avila JA, Adrover JM, Hidalgo A. Neutrophils in Homeostasis, Immunity, and Cancer. Immunity. 2017 Jan 17;46(1):15-28. doi: 10.1016/j.immuni.2016.12.012. — View Citation

Nikolich-Zugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018 Jan;19(1):10-19. doi: 10.1038/s41590-017-0006-x. Epub 2017 Dec 14. Erratum In: Nat Immunol. 2018 Oct;19(10):1146. — View Citation

Oh SJ, Lee JK, Shin OS. Aging and the Immune System: the Impact of Immunosenescence on Viral Infection, Immunity and Vaccine Immunogenicity. Immune Netw. 2019 Nov 14;19(6):e37. doi: 10.4110/in.2019.19.e37. eCollection 2019 Dec. — View Citation

Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-768. doi: 10.1093/cid/ciaa248. — View Citation

Rockx B, Baas T, Zornetzer GA, Haagmans B, Sheahan T, Frieman M, Dyer MD, Teal TH, Proll S, van den Brand J, Baric R, Katze MG. Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection. J Virol. 2009 Jul;83(14):7062-74. doi: 10.1128/JVI.00127-09. Epub 2009 May 6. Erratum In: J Virol. 2009 Sep;83(17):9022. — View Citation

Tachikart Y, Malaise O, Mumme M, Jorgensen C, Brondello JM. Seno-suppressive molecules as new therapeutic perspectives in rheumatic diseases. Biochem Pharmacol. 2019 Jul;165:126-133. doi: 10.1016/j.bcp.2019.03.017. Epub 2019 Mar 13. — View Citation

Vicente R, Mausset-Bonnefont AL, Jorgensen C, Louis-Plence P, Brondello JM. Cellular senescence impact on immune cell fate and function. Aging Cell. 2016 Jun;15(3):400-6. doi: 10.1111/acel.12455. Epub 2016 Feb 22. — View Citation

Wang R, Pan M, Zhang X, Han M, Fan X, Zhao F, Miao M, Xu J, Guan M, Deng X, Chen X, Shen L. Epidemiological and clinical features of 125 Hospitalized Patients with COVID-19 in Fuyang, Anhui, China. Int J Infect Dis. 2020 Jun;95:421-428. doi: 10.1016/j.ijid.2020.03.070. Epub 2020 Apr 11. — View Citation

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available. — View Citation

Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, Xu Y, Tian Z. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 May;17(5):533-535. doi: 10.1038/s41423-020-0402-2. Epub 2020 Mar 19. No abstract available. — View Citation

* Note: There are 25 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Results of phenotypic immunosenescence analyses of COVID-19 patients targeting 5 different immune populations (neutrophils, T lymphocytes, NK lymphocytes, B lymphocytes and monocytes). At inclusion visit
Secondary Comparison of previous results with the results of senescence immunophenotyping in peripheral blood of a reference population with an inflammatory disease (active RA) At inclusion visit
Secondary Comparison of previous results with the results of senescence immunophenotyping in peripheral blood of a reference population of healthy controls. At inclusion visit
Secondary Identification of a specific gene expression of immunosenescence induced in COVID-19 patients, using transcriptomic analysis in the different immune subpopulations previously identified and specific to COVID-19 patients. At inclusion visit
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