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

October 10, 2022 updated by: Assistance Publique - Hôpitaux de Paris

Calprotectin Involvement in Emergency Hematopoiesis Observed in Severe COVID-19

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

55

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Villejuif, France, 94800
        • Gustave Roussy Institut
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Didier BOUSCARY, PhD
        • Sub-Investigator:
          • Caroline CHARLIER-WOERTHER, MD, PhD
        • Sub-Investigator:
          • Tali-Anne SZWEBEL, MD
        • Sub-Investigator:
          • Frédéric PENE, MD, PhD
        • Sub-Investigator:
          • Cherifa CHEURFA, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: COVID-19 patients (group 1)
Patients with a recent diagnosis (<7 days since first symptoms) of moderate or severe COVID-19
Biological: Blood samples
blood
Experimental: Chronic myeloid malignancies (group 2)
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
Biological: Blood samples
blood
Other: Control group (group 3)
Age-matched healthy donors
Biological: Blood samples
blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differential gene expression and epigenetic signature of COVID-19 or leukemic versus normal HSC using CITE-seq and ATAC-seq
Time Frame: 12 months
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ex vivo testing of calprotectin-receptor interaction inhibitor
Time Frame: During the last 6 months of the study
Expression of targeted receptors will be monitored by flow cytometry. Clinically developed compounds that could inhibit calprotectin effects will be tested in vitro.
During the last 6 months of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Gustave Roussy, Cancer Campus, Grand Paris

Investigators

  • Principal Investigator: Michaela FONTENAY, PhD, Assistance Publique - Hôpitaux de Paris
  • Study Director: Eric SOLARY, MD, Gustave Roussy Institut

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2023

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

July 1, 2024

Study Registration Dates

First Submitted

July 5, 2021

First Submitted That Met QC Criteria

July 6, 2021

First Posted (Actual)

July 7, 2021

Study Record Updates

Last Update Posted (Actual)

October 12, 2022

Last Update Submitted That Met QC Criteria

October 10, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP210522
  • 2021-A00674-37 (Other Identifier: ID-RCB Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Myelodysplastic Syndromes

Clinical Trials on Blood samples

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mozambique

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe