Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00595491
Recruitment Status : Recruiting
First Posted : January 16, 2008
Last Update Posted : February 25, 2021
Sponsor:
Collaborators:
National Institutes of Health (NIH)
U.S. Army Medical Research and Development Command
Information provided by (Responsible Party):
Benjamin Medoff, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE January 7, 2008
First Posted Date  ICMJE January 16, 2008
Last Update Posted Date February 25, 2021
Study Start Date  ICMJE January 2008
Estimated Primary Completion Date April 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2016)
airway inflammation [ Time Frame: 1,6, or 24 hours ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2008)
airway inflammation [ Time Frame: hours ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Official Title  ICMJE Inflammatory Cellular Trafficking in Asthma in Response to Segmental Allergen Challenge
Brief Summary 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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Asthma
Intervention  ICMJE 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 Cat or Mite allergen. A test dose of allergen is administered first. This will consist of 2ml allergen at 1/10th the threshold concentration for Cat or DF Mite Allergen or at 1/30th the threshold concentration for DP Mite Allergen. If on visual inspection through the bronchoscope there is no evidence of reaction to the test dose, a 2nd allergen challenge is done in the right middle lobe using 2ml of full-dose allergen. After a 1,6, or 24hr recovery period, a single 2nd bronchoscopy is performed 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. OFDI and endobronchial brushing of the airways will also be performed.
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.
Study Arms  ICMJE 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 14, 2017)
313
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2008)
27
Estimated Study Completion Date  ICMJE July 31, 2024
Estimated Primary Completion Date April 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Having second-hand cigarette smoke exposure or indoor furry pets except in the case of dog, if the subject is not allergic to the dog and the subject has a negative skin test to dog (It is also preferred but not required that dust mite allergic subjects have dust mite-proof encasings 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.
  18. Non-English speakers.
  19. History of coagulopathy, thrombocytopenia, pulmonary hypertension, and/or use of anti-coagulants/anti-platelet drugs.

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 10-19 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 10-19 from (A.) above.
  3. A methacholine PC20 < 16 mg/ml.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Daniel L Hamilos, MD 617-726-5090 dhamilos@partners.org
Contact: Benjamin D Medoff, MD 617-726-6695 bmedoff@partners.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00595491
Other Study ID Numbers  ICMJE 2007-P-001050
NIH 4 R37 AI040618 ( Other Identifier: NIH )
BB-IND 13094 ( Other Identifier: FDA )
W81XWH-16-1-0493 ( Other Grant/Funding Number: U.S. Army Medical Research )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Benjamin Medoff, Massachusetts General Hospital
Study Sponsor  ICMJE Benjamin Medoff
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • U.S. Army Medical Research and Development Command
Investigators  ICMJE
Principal Investigator: Benjamin D Medoff, MD, PhD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date February 2021

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