Specialized Proresolving Mediators in Pneumocystis Jirovecii Pneumonia

Pneumonia, Pneumocystis Clinical Trial

— INFLA-PCP  

Official title:

Specialized Proresolving Mediators Evaluation in Pneumocystis Pneumonia Human Infection : Pilot Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03606252
• Other study ID #: RC31/18/0098
• Secondary ID: 2018-A01062-53
• Status: Completed
• Phase: N/A
• Start date: October 1, 2018
• Est. completion date: March 12, 2020

Study information

• Verified date: February 2022
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate specialized proresolving mediators (SPM) concentrations for the first time in subjects infected with Pneumocystis jirovecii. SPM will be measured in blood and urine in patients with favourable or unfavourable outcome of Pneumocystis pneumonia and in patients colonized by Pneumocystis jirovecii. The hypothesis is that low levels of SPM in the blood could be predictive of a negative outcome of pneumocystosis.

Description:

Pneumocystis pneumonia is a severe fungal disease threatening immunosuppressed subjects such as patients suffering from AIDS, oncohematological diseases or solid organ transplanted patients. The disease is characterized by an important inflammation in the infected lungs which is mainly responsible for lungs lesions. Despite an adequate treatment introduction, mortality is still around 20% which can not be explained by a treatment resistance. Specialized proresolving mediators (SPM), including lipoxins, maresins, protectins and resolvins, are newly described molecules implicated in the active process of inflammation resolution. The investigators hypothesis in this study is that high levels of SPM could be predictive of a good resolution of the harmful inflammation, thus a good evolution of the disease, in adequate pneumocystosis therapy conditions. On the contrary, low levels of SPM could be predictive of an unfavourable outcome despite a treatment targeting Pneumocystis jirovecii

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: March 12, 2020
• Est. primary completion date: March 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient over 18 years old
• Patient with a social security cover.
• Free and informed oral consent given.
• Pneumocystis infection or colonization diagnosed on BAL (Broncho-alveolar liquid) or sputum at Toulouse University hospital Mycology laboratory.
• Adequate Pneumocystis therapy for infected patients (cotrimoxazole).

Exclusion Criteria:

• individuals placed under juridical protection,
• individuals placed under guardianship, or supervision.
• Pregnancy or breastfeeding.

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Pneumocystis

Intervention

Other:
• Blood sampling
6 blood sample, 3 at J0 and 3 at J7 ( 2 tubes EDTA of 7mL, 1 tube Blood RNA of 3 mL)
• urine sampling
2 urine sample (1 at J0 and 1 at J7)

Locations

Country	Name	City	State
France	Institut Fédératif de Biologie (IFB), CHU - Hôpital Purpan	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

References & Publications (8)

Colas RA, Shinohara M, Dalli J, Chiang N, Serhan CN. Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am J Physiol Cell Physiol. 2014 Jul 1;307(1):C39-54. doi: 10.1152/ajpcell.00024.2014. Epub 2014 Apr 2. — View Citation

El Fane M, Sodqi M, Oulad Lahsen A, Chakib A, Marih L, Marhoum El Filali K. [Pneumocystosis during HIV infection]. Rev Pneumol Clin. 2016 Aug;72(4):248-54. doi: 10.1016/j.pneumo.2016.04.004. Epub 2016 Jun 24. Review. French. — View Citation

Gilroy DW, Edin ML, De Maeyer RP, Bystrom J, Newson J, Lih FB, Stables M, Zeldin DC, Bishop-Bailey D. CYP450-derived oxylipins mediate inflammatory resolution. Proc Natl Acad Sci U S A. 2016 Jun 7;113(23):E3240-9. doi: 10.1073/pnas.1521453113. Epub 2016 May 25. — View Citation

Karsten E, Breen E, Herbert BR. Red blood cells are dynamic reservoirs of cytokines. Sci Rep. 2018 Feb 15;8(1):3101. doi: 10.1038/s41598-018-21387-w. — View Citation

Keegan A, Charest K, Schmidt R, Briggs D, Deangelo DJ, Li B, Morgan EA, Pozdnyakova O. Flow cytometric minimal residual disease assessment of peripheral blood in acute lymphoblastic leukaemia patients has potential for early detection of relapsed extramedullary disease. J Clin Pathol. 2018 Jul;71(7):653-658. doi: 10.1136/jclinpath-2017-204828. Epub 2018 Mar 27. — View Citation

Ko Y, Jeong BH, Park HY, Koh WJ, Suh GY, Chung MP, Kwon OJ, Jeon K. Outcomes of Pneumocystis pneumonia with respiratory failure in HIV-negative patients. J Crit Care. 2014 Jun;29(3):356-61. doi: 10.1016/j.jcrc.2013.12.005. Epub 2013 Dec 21. — View Citation

Le Faouder P, Baillif V, Spreadbury I, Motta JP, Rousset P, Chêne G, Guigné C, Tercé F, Vanner S, Vergnolle N, Bertrand-Michel J, Dubourdeau M, Cenac N. LC-MS/MS method for rapid and concomitant quantification of pro-inflammatory and pro-resolving polyunsaturated fatty acid metabolites. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Aug 1;932:123-33. doi: 10.1016/j.jchromb.2013.06.014. Epub 2013 Jun 15. — View Citation

Le Gal S, Robert-Gangneux F, Perrot M, Rouillé A, Virmaux M, Damiani C, Totet A, Gangneux JP, Nevez G. Absence of Pneumocystis dihydropteroate synthase mutants in Brittany, France. Diagn Microbiol Infect Dis. 2013 May;76(1):113-5. doi: 10.1016/j.diagmicrobio.2013.01.018. Epub 2013 Feb 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	14,15-DHET blood level at the inclusio	variation of 14,15-DHET blood level at inclusion between each group	Day 0
Primary	14,15-DHET blood level	variation of 14,15-DHET blood level at day 7 between each group	Day 7
Secondary	14,15-DHET urine level	variation of 14,15-DHET urine level at inclusion ad day 7 between each group	Day 0 and Day 7
Secondary	Specialized Pro-Resolving Mediators in blood	Specialized Pro-Resolving Mediators in blood at inclusion and day 7 between each group	Day 0 and Day 7
Secondary	Specialized Pro-Resolving Mediators in urine	Specialized Pro-Resolving Mediators in urine at inclusion and day 7each between group	Day 0 and Day 7
Secondary	Expression levels of the SPM enzymes	Expression levels of the enzymes implicated in SPM synthesis and catabolism in blood at D0 and day 7	Day 0 and day 7
Secondary	Inflammatory blood profile	Inflammatory blood profile with composite criteria pro-inflammatory and anti-inflammatory cytokines levels measured by flow cytometry	Day 0 and day 7
Secondary	Immune cells profile	immune cell proportions in blood measured by flow cytometry	Day 0 and day 7