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Calprotectin, a Biomarker of COVID-19 Severity (CALPRO) (CALPRO)

Primary Purpose

Severe/Moderate Coronavirus, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes

Status

Not yet recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Blood samples

About this trial

This is an interventional diagnostic trial for Severe/Moderate Coronavirus focused on measuring Calprotectin, hematopoiesis, COVID-19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Criteria for all groups:

Adults ≥ 18 years
Dated and signed inform consent *
- * : written informed consent of relative (trusted person, close family) in case of emergency procedure, by default emergency inclusion notified in medical file and pursuance consent sought.
Affiliation with a social security scheme

Criteria for control group:

Age-matched healthy donors

Criteria for chronic myeloid malignancies:

A diagnosis of low or high-risk myelodysplastic syndromes according to the WHO 2016 classification
A diagnosis of dysplastic or proliferative chronic myelomonocytic leukemia according to WHO 2016

Criteria for COVID-19 patients:

Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19

Exclusion Criteria:

Pregnant women
Minor patient or major under protection
Patients with COVID-19 infection and active cancer or a history of cancer within the last 6 months
Patients with COVID-19 and severe comorbidities including cardiovascular or respiratory diseases, unbalanced diabetes, obesity (IMC >29)
Patient on AME (state medical aid)

Sites / Locations

Gustave Roussy Institut

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Other

Arm Label

COVID-19 patients (group 1)

Chronic myeloid malignancies (group 2)

Control group (group 3)

Arm Description

Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19

Adults with chronic myeloid malignancies including myelodysplastic syndromes with low risk MDS ; high risk MDS according to IPSS-R or with dysplastic or proliferative chronic myelomonocytic leukemia according to WHO2016

Age-matched healthy donors

Outcomes

Primary Outcome Measures

Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq

Hematopoietic stem and progenitor cells from patients with severe or moderate COVID-19 or chronic myeloid malignancies or controls will be purified for analyses of transcriptome and chromatin conformation, and also functionally characterized using in vitro culture systems. Results will be compared between the three groups.

Secondary Outcome Measures

Ex vivo testing of calprotectin-receptor interaction inhibitor

Expression of targeted receptors will be monitored by flow cytometry. Clinically developed compounds that could inhibit calprotectin effects will be tested in vitro.

Full Information

NCT ID

NCT04953312

First Posted

July 5, 2021

Last Updated

October 10, 2022

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Gustave Roussy, Cancer Campus, Grand Paris

1. Study Identification

Unique Protocol Identification Number

NCT04953312

Brief Title

Calprotectin, a Biomarker of COVID-19 Severity (CALPRO)

Acronym

CALPRO

Official Title

Calprotectin Involvement in Emergency Hematopoiesis Observed in Severe COVID-19

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 2023 (Anticipated)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Gustave Roussy, Cancer Campus, Grand Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to provide new insights into the pathophysiology of emergency hematopoiesis detected in severe COVID-19 patients. The investigators aim to explore the ability of calprotectin to induce an immunosuppressive myeloid program at the hematopoietic stem and progenitor cell (HSPC) level, and to identify the receptor(s) involved in this effect. Since patients with a hematological malignancy demonstrate a very high propensity to develop a severe COVID-19, the investigators will explore how HSPCs collected from patients with a myeloid malignancy respond to calprotectin.

Detailed Description

Emergency myelopoiesis in response to SARS-CoV-2 infection produce immunosuppressive myeloid cells with accumulation of immature granulocytes and loss of non-classical monocytes. Excessive release of calprotectin, the dimer of S100A8/A9 alarmins, by immature granulocytes and activated monocytes reflects this situation. A role of calprotectin has been previously described in the initiation and progression of chronic hematological malignancies such as myelodysplastic syndromes. To provide a rationale for the targeting of alarmin-driven signaling pathways and limit the pathogenic inflammatory response to SARS-CoV-2 infection, the role of calprotectin in the production of immunosuppressive cells from the bone marrow hematopoietic stem and progenitors cells needs to be investigated in patients with severe COVID-19 in comparison with patients with chronic myeloid malignancies (such as chronic myelomonocytic leukemia and myelodysplastic syndromes) and with age-mached healthy controls. A comprehensive and integrated multiomics approach will be used to decipher the features of immunosuppressive cells and identify therapeutic targets in deregulated pathways.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe/Moderate Coronavirus, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes, Old Age

Keywords

Calprotectin, hematopoiesis, COVID-19

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

55 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

COVID-19 patients (group 1)

Arm Type

Experimental

Arm Description

Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19

Arm Title

Chronic myeloid malignancies (group 2)

Arm Type

Experimental

Arm Description

Arm Title

Control group (group 3)

Arm Type

Other

Arm Description

Age-matched healthy donors

Intervention Type

Biological

Intervention Name(s)

Blood samples

Intervention Description

blood

Primary Outcome Measure Information:

Title

Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq

Description

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Ex vivo testing of calprotectin-receptor interaction inhibitor

Description

Expression of targeted receptors will be monitored by flow cytometry. Clinically developed compounds that could inhibit calprotectin effects will be tested in vitro.

Time Frame

During the last 6 months of the study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Criteria for all groups: Adults ≥ 18 years Dated and signed inform consent * * : written informed consent of relative (trusted person, close family) in case of emergency procedure, by default emergency inclusion notified in medical file and pursuance consent sought. Affiliation with a social security scheme Criteria for control group: Age-matched healthy donors Criteria for chronic myeloid malignancies: A diagnosis of low or high-risk myelodysplastic syndromes according to the WHO 2016 classification A diagnosis of dysplastic or proliferative chronic myelomonocytic leukemia according to WHO 2016 Criteria for COVID-19 patients: Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19 Exclusion Criteria: Pregnant women Minor patient or major under protection Patients with COVID-19 infection and active cancer or a history of cancer within the last 6 months Patients with COVID-19 and severe comorbidities including cardiovascular or respiratory diseases, unbalanced diabetes, obesity (IMC >29) Patient on AME (state medical aid)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michaela FONTENAY, PhD

Phone

+33 1 58 41 20 04

michaela.fontenay@aphp.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Christelle AUGER

Phone

+33 1 58 41 11 86

christelle.auger@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michaela FONTENAY, PhD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Eric SOLARY, MD

Organizational Affiliation

Gustave Roussy Institut

Official's Role

Study Director

Facility Information:

Facility Name

Gustave Roussy Institut

City

Villejuif

ZIP/Postal Code

94800

Country

France

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nathalie DROIN, PhD

Phone

+33 1 42 11 63 02

nathalie.droin@gustaveroussy.fr

First Name & Middle Initial & Last Name & Degree

Betty LEITE, Engineer

Phone

+33 1 42 11 63 02

GD-UGF@gustaveroussy.fr

First Name & Middle Initial & Last Name & Degree

Didier BOUSCARY, PhD

First Name & Middle Initial & Last Name & Degree

Caroline CHARLIER-WOERTHER, MD, PhD

First Name & Middle Initial & Last Name & Degree

Tali-Anne SZWEBEL, MD

First Name & Middle Initial & Last Name & Degree

Frédéric PENE, MD, PhD

First Name & Middle Initial & Last Name & Degree

Cherifa CHEURFA, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32810439

Citation

Silvin A, Chapuis N, Dunsmore G, Goubet AG, Dubuisson A, Derosa L, Almire C, Henon C, Kosmider O, Droin N, Rameau P, Catelain C, Alfaro A, Dussiau C, Friedrich C, Sourdeau E, Marin N, Szwebel TA, Cantin D, Mouthon L, Borderie D, Deloger M, Bredel D, Mouraud S, Drubay D, Andrieu M, Lhonneur AS, Saada V, Stoclin A, Willekens C, Pommeret F, Griscelli F, Ng LG, Zhang Z, Bost P, Amit I, Barlesi F, Marabelle A, Pene F, Gachot B, Andre F, Zitvogel L, Ginhoux F, Fontenay M, Solary E. Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19. Cell. 2020 Sep 17;182(6):1401-1418.e18. doi: 10.1016/j.cell.2020.08.002. Epub 2020 Aug 5.

Results Reference

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PubMed Identifier

32869342

Citation

Shi H, Zuo Y, Yalavarthi S, Gockman K, Zuo M, Madison JA, Blair C, Woodward W, Lezak SP, Lugogo NL, Woods RJ, Lood C, Knight JS, Kanthi Y. Neutrophil calprotectin identifies severe pulmonary disease in COVID-19. J Leukoc Biol. 2021 Jan;109(1):67-72. doi: 10.1002/JLB.3COVCRA0720-359R. Epub 2020 Sep 1.

Results Reference

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PubMed Identifier

33672040

Citation

Udeh R, Advani S, de Guadiana Romualdo LG, Dolja-Gore X. Calprotectin, an Emerging Biomarker of Interest in COVID-19: A Systematic Review and Meta-Analysis. J Clin Med. 2021 Feb 15;10(4):775. doi: 10.3390/jcm10040775.

Results Reference

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PubMed Identifier

33232303

Citation

Abers MS, Delmonte OM, Ricotta EE, Fintzi J, Fink DL, de Jesus AAA, Zarember KA, Alehashemi S, Oikonomou V, Desai JV, Canna SW, Shakoory B, Dobbs K, Imberti L, Sottini A, Quiros-Roldan E, Castelli F, Rossi C, Brugnoni D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Castagnoli R, Montagna D, Licari A, Marseglia GL, Gliniewicz EF, Shaw E, Kahle DE, Rastegar AT, Stack M, Myint-Hpu K, Levinson SL, DiNubile MJ, Chertow DW, Burbelo PD, Cohen JI, Calvo KR, Tsang JS; NIAID COVID-19 Consortium; Su HC, Gallin JI, Kuhns DB, Goldbach-Mansky R, Lionakis MS, Notarangelo LD. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight. 2021 Jan 11;6(1):e144455. doi: 10.1172/jci.insight.144455.

Results Reference

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PubMed Identifier

33217473

Citation

Bauer W, Diehl-Wiesenecker E, Ulke J, Galtung N, Havelka A, Hegel JK, Tauber R, Somasundaram R, Kappert K. Outcome prediction by serum calprotectin in patients with COVID-19 in the emergency department. J Infect. 2021 Apr;82(4):84-123. doi: 10.1016/j.jinf.2020.11.016. Epub 2020 Nov 17. No abstract available.

Results Reference

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PubMed Identifier

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Citation

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Results Reference

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PubMed Identifier

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Citation

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Results Reference

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PubMed Identifier

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Citation

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Results Reference

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Links:

URL

http://www.gfmgroup.org

Description

Groupe Francophone des Myélodysplasies: GFM is a cooperative group of the French Society of Hematology

Learn more about this trial

Calprotectin, a Biomarker of COVID-19 Severity (CALPRO)

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