Effect of Ozone on Airway Inflammation in Allergic Asthmatics Treated With Omalizumab

NCT00287378 | Terminated DMC

• 2 other identifiers: GCRC-2423HL080337-01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Ozone can cause acute airway inflammation in both asthmatics and normal volunteers. However, in asthmatics ozone can cause episodes of worsening of asthma. We want to learn if chronic allergic response, known as "IgE-induced airway inflammation" is what causes the increased inflammation in response to ozone. To do this we will examine the response to ozone in a group of asthmatics treated with omalizumab, a medicine available and approved for use in people with asthma, or a placebo control. The placebo for this study is inert physiologic saline ("salt water") which contains no omalizumab. Both the omalizumab and the placebo will be administered as an injection under the skin. Omalizumab, also called Xolair, is a humanized monoclonal antibody, which means that it originally was produced in mice, then genetically engineered to look more like human than mouse antibody. Omalizumab inactivates IgE, a protein our own immune systems make as part of allergic reactions. The purpose of this study is to test the hypothesis that omalizumab, by blocking this aspect of allergic reactions, will decrease the number of inflammatory cells in the airway after ozone challenge. We also hypothesize that omalizumab will decrease the effects of ozone on changes in lung function, mucociliary clearance (a measure of how quickly mucus clears form the airway) and airway reactivity. Airway reactivity is a measure of how sensitive the airways are to a medication used to diagnose asthma, called methacholine. We will examine these as additional information we can learn during the course of the study. This is a blinded study, meaning that neither you nor the researchers know if you get the active drug or placebo, but that information can be obtained if needed. The placebo is an injection of inert physiological saline ("salt water") which contains no omalizumab.

Conditions

Asthma; Allergy

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint (increase in airway neutrophils) will be assessed by comparison of the differences between sputum neutrophil influx after ozone (adjusted for post air challenge neutrophils) between omalizumab and placebo treated volunteers

  16 weeks

Secondary Outcomes (3)

• Differences in ozone induced changes in FEV1 and FVC between omalizumab and control groups

  16 weeks

• Differences in mucociliary clearance and airway deposition between omalizumab and control groups

  16 weeks

• Differences in ozone induced changes in sputum eosinophils between omalizumab and control groups

  16 weeks

Study Arms (1)

1

EXPERIMENTAL

Drug: omalizumab

Interventions

omalizumab DRUG

omalizumab as per weight and IgE

Also known as: Xolair

1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Normal lung function, defined as (Knudson 1976/1984 predicted set):
• FVC of \> 80 % of that predicted for gender, ethnicity, age and height
• FEV1 of \> 80 % of that predicted for gender, ethnicity, age and height
• FEV1/FVC ratio of \> 80 % of predicted values
• Evidence of allergy to house dust mite
• Oxygen saturation of \> 94 %
• Normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg)
• Symptom Score (defined in section "f") no greater than 20 (out of a possible 60) for total symptom score with a value no greater than 3 for any one score. No more than one score may be greater or equal than 3.
• IgE within the following ranges and body weights for omalizumab dosing: IgE ≥30-700 int. units/mL, and weight 30-90 kg.

You may not qualify if:

• A history of significant chronic illnesses (to include diabetes, autoimmune diseases, immunodeficiency state, known ischemic heart disease, chronic respiratory diseases such as chronic obstructive pulmonary disease or severe asthma, hypertension)
• Allergy to any medications which may be used in the course of this study (albuterol, acetaminophen, aspirin or non-steroidal anti-inflammatory agents, corticosteroids, lactose, polyethylene glycol)
• Positive pregnancy test at time of initial screening
• Medications which may impact the results of the ozone challenge, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents) or suggest an ongoing illness (such as antibiotics)
• Mega doses of vitamins and supplements, homeopathic/naturopathic medicines
• Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
• Use of systemic steroid therapy within the preceding 12 months.
• Use of inhaled steroids, cromolyn or leukotriene inhibitors (Montelukast or zafirkulast) initiated within the past month (except for use of cromolyn exclusively prior to exercise). Patients must be on a stable regimen of therapy and shown to be stable.
• Use of daily theophylline within the past month.
• Pregnancy or nursing a baby.
• Cigarette smoking \> 1 pack per month.
• Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
• Exacerbation of asthma more than 2x/week which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
• Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institutes of Health (NIH): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Center for Environmental Medicine, Asthma and Lung Biology at the University of North Carolina

Chapel Hill, North Carolina, 27599-7310, United States

Location

Related Links

• Center for Environmental Medicine, Asthma and Lung Biology

MeSH Terms

Conditions

Asthma; Hypersensitivity

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Study Officials

• Terry L Noah, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 3, 2006
• First Posted: February 6, 2006
• Study Start: March 1, 2006
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: June 30, 2009

Record last verified: 2009-02

Locations

US (1)