Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Andrew D. Luster, M.D.,Ph.D., Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00595491
First received: January 7, 2008
Last updated: July 10, 2014
Last verified: July 2014

January 7, 2008
July 10, 2014
January 2008
January 2015   (final data collection date for primary outcome measure)
airway inflammation [ Time Frame: hours ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00595491 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Inflammatory Cellular Trafficking in Asthma in Response to Segmental Allergen Challenge

Asthma is a heterogeneous disorder in which multiple potential inflammatory pathways contribute to airway obstruction. The biological basis for airway inflammation is the subject of intensive investigation. This work is designed to identify airway factors that are responsible for recruiting cells and associate their airway presence with atopy and asthma.

The production of chemotactic cytokines or chemokines by the airways is one of the mechanisms thought to be responsible for the recruitment of inflammatory cells to the airways (Makay 2001). While the chemokine receptor-ligand systems responsible for immune cell homing to the mucosal surface of the gastrointestinal tract have been clarified, those responsible for allergic airway inflammation remain unknown. This work is designed to identify airway factors that are responsible for recruiting cells and associate their airway presence with atopy and asthma.

Interventional
Not Provided
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Asthma
Biological: Bronchoscopy, Segmental Allergen Challenge, and Broncheoalveolar Lavage
Bronchoalveolar lavage is performed in the lingula without instillation of diluent or allergen.A 2ml aliquot of diluent is instilled into the right upper lobe. The procedure is repeated in the right middle lobe with instillation of 2ml of standardized cat or mite allergen solution.A test dose of allergen is administered first.This will consist of 2ml of allergen at 1/10th the threshold allergen concentration.If on visual inspection through the bronchoscope there is no evidence of inflammation,a second segmental allergen challenge is done in the right middle lobe using 2ml of allergen at the threshold concentration.After a 1-4 hr recovery period,a single second bronchoscopy is performed at either 1,4 or 24hrs after delivery of allergen extract and diluent and 1 Tbsp of blood is obtained.Bronchoalveolar lavage will be obtained from the lobes in which the diluent and allergen were instilled.Additional visualization of the airway response will be performed using OFDI.
Other Names:
  • Other Names:
  • One of 3 Standardized allergen extracts will be used:
  • Standardized Cat Hair Extract
  • Standardized mite extract-Dermatophagoides farinae
  • Standardized mite extract-Dermatophagoides pteronyssinus
  • Phenolized saline diluent will also be used in this study.
  • All will be purchased from Greer Laboratories Lenoir,NC.
Experimental: allergic asthmatic, allergic nonasthmatic, healthy
Adults who are allergic asthmatics, allergic nonasthmatics, or healthy controls will receive segmental allergen challenge to the lung
Intervention: Biological: Bronchoscopy, Segmental Allergen Challenge, and Broncheoalveolar Lavage

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
178
January 2018
January 2015   (final data collection date for primary outcome measure)

A. Subjects with Allergic Asthma (AA subjects)

Inclusion Criteria:

  1. All subjects will have a baseline FEV1 determined at the characterization visit that is no less than 75 % of the predicted value.
  2. All subjects will have a clinical history of allergic symptoms to cat or dust mite allergen and demonstrated skin reactivity (a positive allergen prick test).
  3. Life-long absence of cigarette smoking (defined as a lifetime total of less than 5 pack-years); none in 5 years).
  4. Willing and able to give informed consent.
  5. Expressed the desire to participate in an interview with the principal investigator.
  6. Age between 18 and 50 years.

Exclusion Criteria:

  1. Women of childbearing potential who are documented to be pregnant (based on Urine beta-HCG testing), are sexually active and not using contraception, are seeking to become pregnant, or who are nursing.
  2. The presence of spontaneous asthmatic episode or clinical evidence of upper respiratory tract infection within the previous 6 weeks.
  3. Participation in research study involving a drug or biologic during the 30 days prior to the study.
  4. Intolerance to albuterol, atropine, lidocaine, fentanyl, or midazolam.
  5. Antihistamines within 7 days of the screening visit.
  6. Presence of diabetes mellitus, congestive heart failure, ventricular arrhythmias, history of a cerebrovascular accident, renal failure, history of anaphylaxis, or cirrhosis.
  7. Use of systemic steroids, increased use of inhaled steroids, beta blockers and MAO inhibitors or a visit for an asthma exacerbation within 1 month of the screening visit.
  8. Antibiotic use for respiratory disease within 1 month of the characterization visit or a respiratory tract infection within 6 weeks of the bronchoscopy visits.
  9. A history of asthma-related respiratory failure requiring intubation.
  10. Quantitative skin-prick test positive reaction down to an allergen concentration of 0.056 BAU or AU/ml .
  11. Taking beta-adrenergic blocking agents or monoamine oxidase inhibitors.
  12. Subjects with a high possibility of poor compliance with the study.
  13. No history of cigarette smoking within the past 5 years or > 10 pack years total.
  14. No indoor animal or second-hand cigarette smoke exposure. (It is also preferred but not required that dust mite allergic subjects have dust mite-proof encasing on their mattress and pillows.)
  15. Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection.
  16. Use of Xolair (omalizumab - anti-IgE monoclonal antibody) for 6 months.
  17. Immunotherapy with cat or dust mite extract now or in the past.

B. Healthy Normal Control Subjects (NC subjects)

Normal control subjects will be individuals who are in good overall health, age and sex matched to the asthmatic group, age 18 - 50 and nonallergic, i.e. entirely negative on the panel of prick skin tests listed in section V (Study Procedures), with no history of allergic rhinitis or asthma, no history of allergic symptoms caused by cats or dust mite allergen exposure, life-long nonsmokers of cigarettes (defined as a lifetime total of less than 5 pack-years and none in 5 years), normal spirometry (i.e. FEV1 and FVC of at least 90% of predicted) and with a methacholine PC20 of > 16 mg/ml.

Exclusion Criteria:

  1. A history of allergy, asthma, nasal or sinus disease.
  2. Exclusion criteria #1, 3-8 and 10-17 from (A.) above.

C. Allergic Nonasthmatic Subjects (ANA subjects)

Inclusion Criteria:

  1. ANA subjects will have a history of either (a) allergic rhinitis (with one or more of the following symptoms: nasal congestion, sneezing, runny nose, postnasal drainage), (b) allergic conjunctivitis (ocular itching, tearing and/or swelling) or (c) contact allergy associated with cat dander or dust mite and a positive allergy test to the same allergen.
  2. All subjects will have a baseline FEV1 and FVC determined at the characterization visit that is no less than 90 % of the predicted value.
  3. All subjects will have a positive allergy skin prick test to cat dander or dust mite allergen.
  4. All subjects will be in good general health.
  5. Life-long absence of cigarette smoking (defined as a lifetime total of less than 5 pack-years and none in 5 years).
  6. Willing and able to give informed consent.
  7. Expressed the desire to participate in an interview with the principal investigator.
  8. Age between 18 and 50 years.

Exclusion Criteria:

  1. A history of asthma.
  2. Exclusion criteria #1, 3-8 and 10-17 from (A.) above.
  3. A methacholine PC20 < 16 mg/ml.
Both
18 Years to 50 Years
Yes
Contact: Daniel L Hamilos, MD 617-643-2262 dhamilos@partners.org
Contact: Benjamin D Medoff, MD 617-726-6695 bmedoff@partners.org
United States
 
NCT00595491
2007-P-001050, NIH 5 R37 AI040618, FDA: BB-IND 13094
Yes
Andrew D. Luster, M.D.,Ph.D., Massachusetts General Hospital
Andrew D. Luster, M.D.,Ph.D.
Not Provided
Principal Investigator: Andrew D Luster, MD, PhD Massachusetts General Hospital
Massachusetts General Hospital
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP