- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01082952
Role of Eosinophils in the Proliferation of Airway Smooth Muscle (ASM) Cells
Role of Eosinophils in the Proliferation of ASM Cells in Asthma
Study Overview
Status
Conditions
Detailed Description
Rational and hypothesis Asthma is a chronic inflammatory disorder of the lung airways that is associated with airway remodeling and hyperresponsiveness (AHR). Its is well documented that the smooth muscle mass in asthmatic airways is increased due to hypertrophy and hyperplasia of the ASM cells. Moreover, eosinophils have been proposed in different studies to play a major role in airway remodeling. The association between increased eosinophil numbers and asthma severity has been well documented. Here, we hypothesized that the interaction between eosinophils and ASM cells plays an important role in airway remodeling and that eosinophils modulate the airways through enhancing ASM cell proliferation.
Objectives of the study The aim of this study is to examine the effect of eosinophils on ASM cell proliferation using eosinophils isolated from asthmatic subjects.
Specific aim 1. Effect of co-culture of ASM cells with eosinophils on ASM cell proliferation.
In this specific aim, the effect of eosinophil on ASM cell proliferation will be studied by co-culturing eosinophils isolated from asthmatic and healthy patients with ASM cells in vitro. This will be done using non-stimulated eosinophils or eosinophils activated with Interleukin-5 (IL-5)and Interleukin-3 (IL-3). ASM proliferation will be monitored by determining the levels of the proliferation marker Ki-67 expression in ASM cells.
Specific aim 2. Understanding the mechanism by which eosinophils enhance ASM proliferation.
In this specific aim, we will study the mechanism by which eosinophils enhance the proliferation of ASM cells. To study if this effect of eosinophils is done through direct contact with ASM cells, we will co-culture ASM cells with eosinophils membrane fractions. Moreover, we will examine the effect of cytokines and extracellular matrix (ECM) proteins produced by eosinophils on smooth muscle cells
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Riyadh, Saudi Arabia
- Prince Naif center for immunological research
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Asthma: Patient Selection (Inclusion Criteria)
- Subjects with documented clinical history of asthma for a period of at least 6 months prior to study entry (and a minimum of one clinic follow-up visit since initial diagnosis)
- Willing to provide written informed consent and in the judgment of the investigator, individuals who are able to understand the informed consent process.
- Subjects with documented clinical history (in preceding 12 months) of airway reversibility of at least 12% based on Forced Expiratory Volume (FEV1), measured pre and post inhalation of a β-2 agonist (2 puffs of albuterol using a measured dose inhaler with spacer) OR
- Individuals with strong history of asthma but with waning, or no current symptoms may be included in the study if their asthma was well controlled using an asthma medication. Principal investigator must verify or know the clinical history of an individual before accepting him as an asthmatic individual.
- Able to perform Spirometry/FEV1 correctly.
Exclusion Criteria
- Age < 5 years
- Smoking for 20 years, 1 pack/day or more.
- Congestive heart failure.
- Chronic Obstructive Pulmonary Disease (COPD).
- Chronic lung disease other than asthma and COPD.
- Bronchiectasis.
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
Cohorts and Interventions
Group / Cohort |
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Asthmatic patients
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Non asthmatic patients
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fold Increase in ASM Proliferation Following Incubation With Eosinophils.
Time Frame: one day
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Airway Smooth Muscle (ASM) cell proliferation was measured 24 hrs following their co-culture with eosinophil.
This was determined using Ki-67 staining and flowcytometry.
The fold increase in ASM proliferation was then determined.
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one day
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fold Increase in ASM Cells Proliferation Following Treatment With Cysteinyl Leukotrienes
Time Frame: one day
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The effect of Eosinophil release of Cysteinyl Leukotrienes on ASM proliferation was determined using blocking agents.
This was determined using Ki-67 staining and flowcytometry.
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one day
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Saleh Al-Muhsen, MD, King Saud University
- Principal Investigator: Rabih Halwani, PhD, King Saud University
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- effect of eosinophil on ASM
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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