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

This study has been terminated.
(lack of enrollment)
Sponsor:
Collaborators:
Genentech
Information provided by:
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00287378
First received: February 3, 2006
Last updated: June 26, 2009
Last verified: February 2009
  Purpose

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.


Condition Intervention
Asthma
Allergy
Drug: omalizumab

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Effect of Ozone on Airway Inflammation in Allergic Asthmatics Treated With Omalizumab

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • 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 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Differences in ozone induced changes in FEV1 and FVC between omalizumab and control groups [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Differences in mucociliary clearance and airway deposition between omalizumab and control groups [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Differences in ozone induced changes in sputum eosinophils between omalizumab and control groups [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: March 2006
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: omalizumab
omalizumab as per weight and IgE
Other Name: Xolair

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • Acute, non-chronic, medical conditions, including (but not limited to) pneumonia or bronchitis requiring antibiotics, febrile illnesses, flu-like symptoms must be totally resolved symptomatically for 2 weeks. Documentation of normal lung function (as defined in "Specific Inclusion Criteria") must be met.
  • Unspecified illnesses, which in the judgment of the investigator increase the risk associated with ozone inhalation challenge, will be a basis for exclusion.
  • 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).
  • Dosing level of an inhaled steroid must be consistent with mild episodic asthma as outlined by the NHLBI NAEPP guidelines. Any dose of inhaled steroid typically used for moderate or severe asthma will result in exclusion from the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00287378

Locations
United States, North Carolina
Center for Environmental Medicine, Asthma and Lung Biology at the University of North Carolina
Chapel Hill, North Carolina, United States, 27599-7310
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Genentech
Investigators
Principal Investigator: Terry L Noah, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
No publications provided

Responsible Party: Barbara Longmire, Director Office of Clinical Trials, University of North Carolina at Chapel Hill
ClinicalTrials.gov Identifier: NCT00287378     History of Changes
Other Study ID Numbers: GCRC-2423, HL080337-01
Study First Received: February 3, 2006
Last Updated: June 26, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Asthma
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Omalizumab
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on July 20, 2014