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Effect of in Vitro Blocking the Common Beta Chain on Cell Viability in Asthma

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01759849
First Posted: January 3, 2013
Last Update Posted: July 13, 2017
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. Read our disclaimer for details.
Collaborator:
CSL Limited
Information provided by (Responsible Party):
Hamilton Health Sciences Corporation
  Purpose
This study examines in vitro blockade of signaling through the β-chain, on viability, activation and differentiation of eosinophils and their progenitors collected in sputum, blood and bone marrow samples pre and post-allergen challenge from mild atopic asthmatic subjects.

Condition Intervention
Asthma Other: Allergen

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effect of in Vitro Blocking the Common Beta Chain on the Function of Blood, Bone Marrow and Sputum Cells Collected From Asthmatic Donors.

Further study details as provided by Hamilton Health Sciences Corporation:

Primary Outcome Measures:
  • Sputum Collection [ Time Frame: 7 hours post allergen ]
    Three baseline sample collections will ensure sufficient numbers of cells are collected for proposed outcomes. Post allergen cells will be examined at time points when these populations are known to be at their highest frequency.


Biospecimen Retention:   Samples Without DNA
Blood, bone marrow and induced sputum.

Enrollment: 10
Study Start Date: November 2012
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Allergen challenge
Determination of the effects of a β-chain monoclonal antibody (MAb) on the function of cells naturally activated by in vivo allergen exposure, from donors with allergen-induced asthma
Other: Allergen
Allergen extract is administered by inhalation.

Detailed Description:

The experiments will use sputum samples induced from subjects with mild asthma, undergoing allergen inhalation challenges. In general, each sample will be composed of >10% neutrophils and >10% macrophages. Samples collected pre-allergen will have a low frequency of eosinophils and lymphocytes (<1%), however the percentage of eosinophils will increase to approximately 12% following allergen challenges. The sputum samples will be processed in DPBS (without dithiothreitol), and the cell suspension will be adjusted to 1 million cells/ml in DMEM with penicillin and streptomycin. A cytospin will be made for differential cell counts. The mixed cell population at 5 million cells/ml will be incubated for 48 hours at 37 degrees Celcius ± β-chain MAb at a concentration of 100 mcg/ml. After 48 hours the cell culture medium will be removed for assay of cytokines and chemokines by ELISA. Cells will be resuspended in PBS and Binding Buffer (BD Pharmingen, Cat no. 556454),stained for assessments by flow cytometry, and analyzed in duplicate.

Experiments will use blood (80 ml) and bone marrow aspirates (5ml) from atopic asthmatics taken pre and 24hr post allergen challenge. Methylcult micro-culture colonogenic assays will be performed to enumerate outgrowth of Eo/Baso-CFU and GM-CFU from CD34+ cells populations collected from the blood and bone marrow samples. Methylcult assays will be performed with CD34+ enriched cell populations in the presence of IL-5,IL-3 and GM-CSF +/- CSL311. Following 14 days culture, colonies will be enumerated.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Subjects with mild allergic asthma.
Criteria

Inclusion Criteria:

  • Male and female volunteers 18 through 65 years of age.
  • General good health
  • Mild to moderate, stable, allergic asthma
  • History of episodic wheeze and shortness of breath; FEV1 at baseline at least 70% of the predicted value
  • Able to understand and give written informed consent and has signed a written informed consent form approved by the investigator's REB
  • Positive methacholine challenge
  • Positive skin-prick test to common aeroallergens (including cat, dust mite, grass, pollen)
  • Positive allergen-induced airway bronchoconstriction (a fall in FEV1 of at least 20% from baseline)

Exclusion Criteria:

  • A worsening of asthma or a respiratory tract infection within 6 weeks preceding study entry
  • Use of corticosteroids, immunosuppressives, anticoagulants (warfarin or heparin) within 28 days prior to randomization into the study
  • Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of dosing or aspirin with 7 days of dosing
  • Have chronic use of any other medication for treatment of allergic lung disease other than short- and intermediate-acting ß2-agonists or ipratropium bromide
  • Use of caffeine-containing products or medications for 12 hours or alcohol or over the counter drugs including aspirin, cold and allergy medications for 48 hours or inhaled bronchodilators for 8 hours prior to methacholine and allergen challenges
  • Use of tobacco products of any kind currently or within the previous 12 months, or smoking history > 10 pack years.
  • Lung disease other than mild to moderate allergic asthma
  • Unwillingness or inability to comply with the study protocol for any other reason.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01759849


Locations
Canada, Ontario
McMaster University Medical Center
Hamilton, Ontario, Canada, L8N 3Z5
Sponsors and Collaborators
Hamilton Health Sciences Corporation
CSL Limited
Investigators
Principal Investigator: Gail M Gauvreau, PhD Hamilton Health Sciences Corporation
  More Information

Additional Information:
Responsible Party: Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier: NCT01759849     History of Changes
Other Study ID Numbers: Bc in vitro study
First Submitted: December 17, 2012
First Posted: January 3, 2013
Last Update Posted: July 13, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hamilton Health Sciences Corporation:
Asthma
β-chain signaling
allergen inhalation challenges
sputum
bone marrow aspirate
blood collection
-methacholine challenge

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases