Identification of Serum Biomarkers for CD15+ Hypodense Neutrophils in Severe Asthma

Severe Persistent Asthma Clinical Trial

Official title:

Identification of Serum Biomarkers for CD15+ Hypodense Neutrophils in Severe Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02659618
• Other study ID #: ML29345
• Status: Completed
• Start date: April 2016
• Est. completion date: December 16, 2020

Study information

• Verified date: December 2020
• Source: Rush University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this study is to identify a serum biomarker(s) that can detect increased levels of a population of CD15+ hypodense neutrophils termed low-density granulocytes (LDG) in the blood of patients with severe persistent asthma.

Description:

Neutrophils are implicated in the pathophysiology of multiple asthma phenotypes. It was shown in study IST Q4935s that low-density granulocytes (LDG) are elevated in the blood of patients with moderate or severe asthma. The greatest frequency and the highest percentages of LDG were observed in subjects with severe asthma. The LDG, which were first identified and characterized in systemic lupus erythematosus (SLE) patients, have been reported to display increased cytotoxicity for endothelial cells, increased tendency to form neutrophil extracellular traps, and increased production of tumor necrosis factor (TNF). It was also observed that the LDG expressed increased levels of CD15, which can facilitate attachment of activated platelets to the LDG. Identification of a putative serum biomarker that correlates with increased levels of the CD15+ LDG may be useful for the detection of neutrophil-associated inflammation in severe asthma. Thirty subjects will be screened to identify 20 subjects with severe persistent asthma. The following data and/or samples will then be obtained within three weeks of the clinical assessment: (1) the percentages of LDG will be quantified by flow cytometry; (2) a blood sample will be collected into a PAXgene Blood tube and stored until shipped to Genentech for gene profiling analysis; and (3) a serum sample will be collected for measurement of total immunoglobulin E (IgE) and for future confirmation of potential biomarkers identified in the gene profiling analyses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 16, 2020
• Est. primary completion date: September 26, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

• Physician diagnosis of severe persistent asthma;
• Positive skin test or radioallergosorbent test (RAST) for an aeroallergen;
• Male or female age 12-65 years;
• Non-smoker.

Exclusion Criteria:

• Asthma exacerbation requiring treatment with or increase in oral corticosteroids within 30 days prior to the study;
• Respiratory infection within 30 days prior to the study;
• Starting or requiring a change in allergen immunotherapy within 30 days prior to the study;
• Having been treated with Xolair within the past year;
• Requiring chronic immunosuppressive therapy;
• Having taken methotrexate, gold salts, cyclosporine, or macrolide antibiotics within 3 months prior to study;
• Having taken an investigational drug within 30 days prior to the study;
• Have a history of drug or alcohol abuse;
• Pregnancy

Related Conditions & MeSH terms

• Asthma
• Severe Persistent Asthma

Locations

Country	Name	City	State
United States	University Consultants in Allergy/Immunology	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Rush University Medical Center	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of low density granulocytes (LDG) in the peripheral blood mononuclear cell (PBMC)		Visit 1 day
Primary	mRNA levels in severe asthmatics as analyzed by gene profiling analysis	Messenger ribonucleic acid (mRNA) expression levels for blood leukocyte proteins.	Visit 1 day
Secondary	Number of Participants with elevated LDG levels in severe asthmatics using gene profiling analysis on a single PAXgene tube sample		Visit 1 day
Secondary	Serum samples will be collected and analyzed for measurement of total IgE	Correlation between LDG in severe asthma and biomarkers identified in gene profiling analysis	Visit 1 day