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

• ClinicalTrials.gov Identifier: NCT02659618
• Recruitment Status: Unknown
• First Posted: January 20, 2016
• Last Update Posted: September 20, 2018
• Sponsor: Rush University Medical Center
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Mary Tobin, Rush University Medical Center

Tracking Information

• First Submitted Date: July 6, 2015
• First Posted Date: January 20, 2016
• Last Update Posted Date: September 20, 2018
• Study Start Date: April 2016
• Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2016)

• Percentage of low density granulocytes (LDG) in the peripheral blood mononuclear cell (PBMC) [ Time Frame: Visit 1 day ]
• mRNA levels in severe asthmatics as analyzed by gene profiling analysis [ Time Frame: Visit 1 day ]
  Messenger ribonucleic acid (mRNA) expression levels for blood leukocyte proteins.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 19, 2016)

• Number of Participants with elevated LDG levels in severe asthmatics using gene profiling analysis on a single PAXgene tube sample [ Time Frame: Visit 1 day ]
• Serum samples will be collected and analyzed for measurement of total IgE [ Time Frame: Visit 1 day ]
  Correlation between LDG in severe asthma and biomarkers identified in gene profiling analysis

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Identification of Serum Biomarkers for CD15+ Hypodense Neutrophils in Severe Asthma
• Official Title: Identification of Serum Biomarkers for CD15+ Hypodense Neutrophils in Severe Asthma
• 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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Venous blood and serum will be drawn and shipped to Genentech for analysis.

• 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.
• Condition: Severe Persistent Asthma
• Intervention: Not Provided

Study Groups/Cohorts

Severe Persistent Asthma

All subjects will have severe persistent asthma diagnosed by a doctor.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 19, 2016): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2020
• Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02659618
• Other Study ID Numbers: ML29345
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Mary Tobin, Rush University Medical Center
• Study Sponsor: Rush University Medical Center
• Collaborators: Genentech, Inc.
• Investigators: Not Provided
• PRS Account: Rush University Medical Center
• Verification Date: September 2018