AsthmaNCT01082952
Role of Eosinophils in the Proliferation of Airway Smooth Muscle (ASM) Cells
An observational study of Asthma, run by King Saud University at 1 site in Saudi Arabia.
Trial summary
Being a key player in Asthma, eosinophils constitute a potential target to interfere with the series of biological events leading to Asthma pathogenesis. In this proposal, the investigators hypothesize that the interaction between eosinophils and airway smooth muscle cells (ASM) cells plays an important role in airway… Read more about this study
- Who is it for?
- Ages 14 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- How many people
- 12 participants
- Where
- 1 siteSaudi Arabia
- Study dates
- Jan 2010to Jul 2011
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 35 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: 12 patients per group
Who may be able to join
None listed.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Saudi Arabia1 site
Prince Naif center for immunological research
Riyadh, Riyadh Region
About this study
Official title: Role of Eosinophils in the Proliferation of ASM Cells in Asthma
Being a key player in Asthma, eosinophils constitute a potential target to interfere with the series of biological events leading to Asthma pathogenesis. In this proposal, the investigators hypothesize that the interaction between eosinophils and airway smooth muscle cells (ASM) cells plays an important role in airway remodeling. Hence the investigators will investigate the role of eosinophils in enhancing ASM cells proliferation resulting in airways remodeling. The investigators will also investigate the mechanism behind this phenomenon. This will then pave the way for medical (drug) interference at one or several sites in order to prevent one of the main potential reasons behind airway remodeling, namely eosinophil-derived ASM proliferation.
Read the 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
- Conditions
- Asthma
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Asthmatic patients | Not described | |
| Non asthmatic patients | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fold Increase in ASM Proliferation Following Incubation With Eosinophils.
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.
Measured: one day
Secondary outcomes (1)
Fold Increase in ASM Cells Proliferation Following Treatment With Cysteinyl Leukotrienes
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.
Measured: one day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2010 (estimated)
- Study startJan 2010
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- King Saud University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Saleh Zaid Al-Muhsen, King Saud University
- Investigators
- Saleh Al-Muhsen, MD, Study chair, King Saud UniversityRabih Halwani, PhD, Principal investigator, King Saud University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01082952
- Sponsor's protocol ID
- effect of eosinophil on ASM
- Status last verified
- Oct 2011
- First submitted
- 8 Mar 2010
- Last updated
- 18 Nov 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Eosinophils in the Proliferation of ASM Cells in Asthma
- ClinicalTrials.gov ID
- NCT01082952
- Acronym / sponsor ID
- effect of eosinophil on ASM
- Conditions
- Asthma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- King Saud UniversityUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 9 Mar 2010 (estimated)
- Results
- Posted 18 Nov 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Being a key player in Asthma, eosinophils constitute a potential target to interfere with the series of biological events leading to Asthma pathogenesis. In this proposal, the investigators hypothesize that the interaction between eosinophils and airway smooth muscle cells (ASM) cells plays an important role in airway remodeling. Hence the investigators will investigate the role of eosinophils in enhancing ASM cells proliferation resulting in airways remodeling. The investigators will also investigate the mechanism behind this phenomenon. This will then pave the way for medical (drug) interference at one or several sites in order to prevent one of the main potential reasons behind airway remodeling, namely eosinophil-derived ASM proliferation.
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 design
- Observational model
- Case-control
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Asthmatic patients | – | – |
| Non asthmatic patients | – | – |
Who may qualify
- Ages
- 14 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- 12 patients per group
Key inclusion criteria (0 listed)
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Fold Increase in ASM Proliferation Following Incubation With Eosinophils.
Time frame: one day
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.
1 secondary outcome
Fold Increase in ASM Cells Proliferation Following Treatment With Cysteinyl Leukotrienes
Time frame: one day
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saleh Al-Muhsen, MD study chair
King Saud University
Rabih Halwani, PhD principal investigator
King Saud University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma, run by King Saud University at 1 site in Saudi Arabia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fold Increase in ASM Proliferation Following Incubation With Eosinophils. (time frame: one day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2011.