Clinical trial NCT02659618: Identification of Serum Biomarkers for CD15+ Hypodense Neutrophils in Severe Asthma
Official title: Identification of Serum Biomarkers for CD15+ Hypodense Neutrophils in Severe Asthma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Severe Persistent Asthma
Keywords: Asthma
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2016-01-20
Enrollment: 20
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Thirty prospective subjects will be screened to identify 20 subjects with severe persistent asthma. These subjects will be recruited from the Allergy/Immunology outpatient clinic at Rush University Medical Center along with self-referral through advertising posted on campus.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of low density granulocytes (LDG) in the peripheral blood mononuclear cell (PBMC)
timeFrame: Visit 1 day
measure: mRNA levels in severe asthmatics as analyzed by gene profiling analysis
timeFrame: Visit 1 day
Secondary outcomes:
measure: Number of Participants with elevated LDG levels in severe asthmatics using gene profiling analysis on a single PAXgene tube sample
timeFrame: Visit 1 day
measure: Serum samples will be collected and analyzed for measurement of total IgE
timeFrame: Visit 1 day
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University Consultants in Allergy/Immunology
state: Illinois
Study officials:
References: