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Eosinophil Induced Remodelling in Asthma (ERA)

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ClinicalTrials.gov Identifier: NCT02648074
Recruitment Status : Unknown
Verified January 2016 by Kestutis Malakauskas, Lithuanian University of Health Sciences.
Recruitment status was:  Recruiting
First Posted : January 6, 2016
Last Update Posted : January 6, 2016
Sponsor:
Collaborators:
Research Council of Lithuania
University of Groningen
Information provided by (Responsible Party):
Kestutis Malakauskas, Lithuanian University of Health Sciences

Brief Summary:

Asthma is a chronic, inflammatory disease of the lung characterized by intermittent airway obstruction, airway hyperresponsiveness, presence of activated inflammatory cells, inflammatory mediators, and airway structural changes. Airway smooth muscle (ASM) cells actively participate in the remodelling and inflammatory processes through proliferation, release of proinflammatory cytokines, chemokines, and extracellular matrix (ECM) proteins. Eosinophils as essential inflammatory cells may be of importance in ASM remodelling. It is known that eosinophil induces ASM cells proliferation via the secretion of cysteinyl leukotrienes in asthmatics. However there is a possible direct eosinophil-ASM cells functional interaction by adhesion processes. It has been shown that integrins modulate ASM proliferation and contractile protein expression demonstrating allergen-induced ASM remodelling in an animal model of allergic asthma.

Wingless/integrase-1 (WNT) signaling regulates not only a wide range of developmental processes, but its aberrant activation can lead to disease. Recently, it was confirmed that genes polymorphisms in the WNT signaling pathway are associated with impaired lung function in childhood asthma. It was also found for the first time a relevant role of noncanonical WNT signaling in TGFβ-induced ECM expression by ASM cells and identified WNT-5A is the most abundant WNT ligand with increased expression in asthmatics. It demonstrates that WNT-5A could contribute to remodelling of the airways. Unfortunately, the effect of eosinophil on WNT secretion by ASM cells at present is unknown.

Despite the widely acknowledged significance of eosinophils in asthma pathogenesis, the mechanism of eosinophil induced ASM remodelling is unsolved.


Condition or disease Intervention/treatment Phase
Allergic Asthma Airway Remodelling Procedure: Bronchial challenge with allergen Other: Co-culture formation Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Eosinophil Induced Airway Smooth Muscle Remodelling in Asthma
Study Start Date : March 2014
Estimated Primary Completion Date : October 2016
Estimated Study Completion Date : January 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Allergic asthma
Bronchial asthma and sensitization to D. pteronyssinus allergen Interventions: Bronchial challenge with allergen; Eosinophil and linear bronchial smooth muscle cell co-culture formation.
Procedure: Bronchial challenge with allergen
Bronchial challenge is performed with D. pteronyssinus allergen.

Other: Co-culture formation
Eosinophil and linear bronchial smooth muscle cell co-culture formation. Airway smooth muscle cell proliferation, eosinophil adhesion to the bronchial smooth muscle cells, the role of eosinophil integrins in the airway remodelling process is assessed in individual formed co-culture

Active Comparator: Healthy subjects

Healthy subjects without allergic and other chronic respiratory diseases (control group).

Interventions: Bronchial challenge with allergen; Eosinophil and linear bronchial smooth muscle cell co-culture formation.

Procedure: Bronchial challenge with allergen
Bronchial challenge is performed with D. pteronyssinus allergen.

Other: Co-culture formation
Eosinophil and linear bronchial smooth muscle cell co-culture formation. Airway smooth muscle cell proliferation, eosinophil adhesion to the bronchial smooth muscle cells, the role of eosinophil integrins in the airway remodelling process is assessed in individual formed co-culture




Primary Outcome Measures :
  1. Eosinophils and bronchial smooth muscle cell adhesion change assessment [ Time Frame: In 30, 45, 60, 120, 240 minutes time points after eosinophils and bronchial smooth muscle cell interactions start ]
    There are used the individual eosinophil and airway smooth muscle cell co-culture. It is compared the strength of eosinophil adhesion to the bronchial smooth muscle cells in patients with asthma and healthy.

  2. Bronchial smooth muscle cell proliferation change assessment by cell viability [ Time Frame: In 48 and 72 hrs time points after eosinophils and linear bronchial smooth muscle co-culture formation ]
    Bronchial smooth muscle cell proliferation is assessed by cell viability


Secondary Outcome Measures :
  1. The change of capacity of eosinophils' integrins to inhibit the bronchial smooth muscle cell proliferation in patients with asthma [ Time Frame: In 48 and 72 hrs time points after eosinophils and linear bronchial smooth muscle co-culture formation ]
    Using the same eosinophils and linear bronchial smooth muscle cell culture, but in this measure is added integrins

  2. The change of eosinophils' integrins interaction with bronchial smooth muscle cells and Wnt-5A protein production after allergen challenge [ Time Frame: Up to 72 hrs time points after eosinophils (collected from blood of patients before and after bronchial provocation with an allergen) and linear bronchial smooth muscle co-culture formation ]
    The results are compared with the before and after bronchial provocation with Dermatophagoides pteronyssinus allergen. It is measured the integrins as specific adhesion molecules attachments to the bronchial smooth muscle cells after allergen challenge



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men and women between the ages of 18-50 years;
  2. Allergic asthma and sensitization to house dust mites (D. pteronyssinus) allergen, approved with:

    2.1. Medical history and symptoms more than one year and 2.2. skin prick test positive for D. pteronyssinus (positive wheals are those exceeding 3mm in diameter greater than the negative control) and 2.3. Positive bronchial challenge with methacholine or documented completely reversible bronchial obstruction;

  3. Stable lung function (FEV1≥70 perc.);
  4. Postmenopausal women. Premenopausal women if pregnancy test is negative and they agree to use an effective contraceptive measures during the study;
  5. Healthy subjects without allergic and other chronic respiratory diseases (control group);
  6. Non- smokers;
  7. Participants who gave his/her informed written consent.

Exclusion Criteria:

  1. Asthma exacerbation 1 month prior to study
  2. Clinically significant permanent allergy symptoms (ex. cat or dog dander induced allergy)
  3. Contraindications to perform an allergy skin test and/or bronchial provocation test 3.1. Active airway infection 1 month prior the study; 3.2. Used medicaments: 3.2.1. Inhaled glucocorticoids intake 1 month prior the study; 3.2.2. Antihistamines intake 7 days prior the study; 3.2.3. Short acting β2 agonists 12 hours prior the study; 3.2.4. Long acting β2 agonists 2 days prior the study; 3.2.5. Leukotriene receptor antagonists prior 14 days;
  4. If the histamine mean wheal diameter is <= 3 mm or control mean wheal diameter is >= 3 mm;
  5. Contraindications for epinephrine;
  6. Other significant mental and / or internal diseases and conditions, which could be as exclusion criteria due to the opinion of the researcher;
  7. Alcohol or narcotic abuse;
  8. Pregnancy;
  9. Breast-feeding.

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): NCT02648074


Contacts
Contact: Kestutis Malakauskas, Prof., dr. +370-37-326737 kestutis.malakauskas@lsmuni.lt
Contact: Virginija Kalinauskaite-Zukauske, MD +370-686-33551 virgucee@gmail.com

Locations
Lithuania
Lithuanian University of Health Sciences, Pulmonology and Immunology Department Recruiting
Kaunas, Lithuania, LT-50009
Contact: Raimundas Sakalauskas, Prof., dr.    +370-37-326953    raimundas.sakalauskas@kaunoklinikos.lt   
Contact: Kestutis Malakauskas, Prof., dr.    +370-37-326737    kestutis.malakauskas@lsmuni.lt   
Sponsors and Collaborators
Lithuanian University of Health Sciences
Research Council of Lithuania
University of Groningen
Investigators
Study Chair: Kestutis Malakauskas, Prof., dr. Lithuanian University of Health Sciences, Pulmonology and Immunology Department

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kestutis Malakauskas, Prof. dr., Lithuanian University of Health Sciences
ClinicalTrials.gov Identifier: NCT02648074     History of Changes
Other Study ID Numbers: MIP-010/2014
PSUL-010/2014 ( Other Identifier: Lithuanian University of Health Sciences )
First Posted: January 6, 2016    Key Record Dates
Last Update Posted: January 6, 2016
Last Verified: January 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Kestutis Malakauskas, Lithuanian University of Health Sciences:
asthma
eosinophils
airway smooth muscle
airway remodelling
integrins
cytokines

Additional relevant MeSH terms:
Asthma
Airway Remodeling
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathological Conditions, Anatomical