Allergic AsthmaNCT04542902
Non-coding RNAs Analysis of Eosinophil Subtypes in Asthma
A study testing Dermatophagoides pteronyssinus allergen, Blood sampling and Bronchial challenge with allergen in people with Allergic Asthma and Severe Eosinophilic Asthma, run by Lithuanian University of Health Sciences at 1 site in Lithuania.
Trial summary
Chronic airway inflammation rich in eosinophils is an important feature seen in asthma. Airway and blood eosinophilia is associated with increased rates of asthma exacerbations and more intense treatment. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Allergic Asthma, Severe Eosinophilic Asthma
- What is being tested?
- Dermatophagoides pteronyssinus allergen, Blood sampling and Bronchial challenge with allergen
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteLithuania
- Study dates
- 1 Oct 2020to 1 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and women between the ages of 18-70 years;
- Allergic asthma and sensitization to house dust mites (D. pteronyssinus) allergen, approved with: 1) medical history and symptoms more than one year; 2) skin prick test positive for D. pteronyssinus (positive wheals are those exceeding 3 mm in diameter greater than the negative control); 3) positive bronchial challenge with methacholine or documented reversible bronchial obstruction;
- Severe eosinophilic asthma;
- Premenopausal women if pregnancy test is negative;
- Healthy subjects without allergic and other chronic respiratory diseases (control group);
- Participants who gave his/her informed written consent.
Who cannot join
- Asthma exacerbation 1 month prior to study;
- Clinically significant permanent allergy symptoms (ex. cat or dog dander induced allergy);
- Contraindications to perform an allergy skin test and/or bronchial provocation test: 1) active airway infection 1 month prior the study; 2) used medicaments: inhaled glucocorticoids intake 1 month prior the study, antihistamines intake 7 days prior the study; 3) short acting β2 agonists 12 hours prior the study; 4) long acting β2 agonists 2 days prior the study; 5) leukotriene receptor antagonists prior 14 days;
- Contraindications for epinephrine;
- Other significant mental and / or internal diseases and conditions, which could be as exclusion criteria due to the opinion of the researcher;
- Alcohol or narcotic abuse;
- Pregnancy;
- Breast-feeding.
Trial locations and contacts
1 site in 1 country.
Lithuania1 site, 1 recruiting
- Recruiting
Lithuanian University of Health Sciences, Pulmonology Department
Kaunas, LT-50009
Kęstutis Malakauskas, Prof., Dr., +37037326737, kestutis.malakauskas@lsmuni.lt
About this study
Chronic airway inflammation rich in eosinophils is an important feature seen in asthma. Airway and blood eosinophilia is associated with increased rates of asthma exacerbations and more intense treatment.
Recently, the existence of two distinct eosinophils subtypes was revealed-lung-resident eosinophils (rEOS), which maturate independently to interleukin (IL) 5, with the primary function to maintain tissue homeostasis, and inflammatory eosinophils (iEOS), which mature in IL-5-dependent manner and are mainly involved in immune responses. Eosinophils' effect on the airway remodeling in asthma depends not only on the activity but also by their viable number in the lungs. Blood iEOS infiltrate the airways mainly after the environmental stimulus like allergen and leave the airways with bronchial secretions. However, rEOS reside lung tissue for their entire lifetime regulating local immunity. Blood rEOS and iEOS ratio alters in asthma, compared with healthy controls. It is known that the predominant eosinophils subtype in allergic asthma are iEOS, while rEOS are basic subtype in severe eosinophilic asthma patients, moreover, they are different in adhesive properties and survivability as well. Distinct biological properties allows to speculate about their different functions in asthma, however, there are still little information. Data about differently expressed microRNA (miRNA) profiles in eosinophils in asthma suggests, that eosinophils subtypes can be distinct in non-coding RNA (ncRNA) - microRNA (miRNA), piwi-interacting RNA (piRNA) and long non-coding RNA (IncRNA) profiles that could describe their role in asthma pathogenesis and act as biomarkers to discern asthma phenotypes.
Read the detailed description
Asthma is not cured, and only well-balanced treatment can control the course and severity of the disease. Most clinical symptoms rise from aberrant chronic airway inflammation mostly eosinophilic. Eosinophils are terminally differentiated granulocytes that actively contribute to innate and adaptive inflammatory cascades through the production and release of diverse chemokines, cytokines, lipid mediators and other growth factors. IL-5 plays a fundamental role in eosinophils maturation in the bone marrow, their recruitment, and activation at sites of inflammation.
Historically eosinophils were described as a critical player in host defense, including parasites, viruses, fungi, or bacteria, giving them a destructive inflammatory cell label. However, it became clear that steady-state eosinophils can contribute to the immunoregulation and tissue homeostasis as well. Studies revealed that there are distinct eosinophils subtypes - immunoregulatory lung-resident eosinophils (rEOS) and inflammatory eosinophils (iEOS), involved in immune responses. Distinct eosinophils subtypes with different functions determines the separate treatment. There are still only a few studies describing distinct eosinophils subtypes in the lungs or blood. It is the beginning of a new promising research area for better individualized eosinophilic asthma treatment, moreover, other eosinophilic diseases as well.
Peripheral blood eosinophils studies are sufficiently relevant to the tissue eosinophils studies, as blood eosinophils are released into the bloodstream in a fully maturated form. Moreover, peripheral blood study could give additional information with possibilities to prevent eosinophils effects in the early stage, before migration to the airways. Furthermore, the existence of tissue-resident eosinophils in peripheral blood is confirmed and primary research for eosinophil subtypes surface markers was made according to the data of human blood eosinophils.
Data about differently differently expressed microRNA (miRNA) profiles in eosinophils in asthma suggests, that eosinophils subtypes can be distinct in non-coding RNA (ncRNA) - microRNA (miRNA), piwi-interacting RNA (piRNA) and long non-coding RNA (IncRNA) profiles that could describe their role in asthma pathogenesis and act as biomarkers to discern asthma phenotypes.
Researchers have plan to expand research by analyzing non-coding RNA (ncRNA) - miRNA, piRNA and lncRNA profiles of rEOS and iEOS as well as selected ncRNA signatures in blood plasma estimating their diagnostic value. Moreover, additional investigation of ncRNA in eosinophil-derived exosomes will provide important data about possible effect of eosinophils subtypes on airway remodeling via secreted ncRNA. ncRNAs are key regulators for gene transcription. However, there is evidence about their dysregulation in eosinophils during asthma. It will give important information about molecular signaling pathways that regulate the activity of distinct eosinophil subtypes during health and asthma, and provide the essential information about possible new therapeutic targets for their control. Additionally researchers will investigate the biological differences between rEOS and iEOS, including surface integrins and eosinophilopoietins receptors expression, adhesive properties, survivability, synthesized reactive oxygen species and apoptosis, as well as their effect on pulmonary structural cells physiological activity as proliferation, apoptosis, migration, contractility and proteins production, and will relate it with molecular signaling pathways, regulated by distinct expressed ncRNAs. ncRNAs can be stored in eosinophils exosomes and expressed to the surrounding environment. Information about ncRNAs in eosinophils-derived exosomes will demonstrate their function by affecting the other cells, especially after migration to airways. Moreover, ncRNAs are stable and resistant to blood RNases and differentially expressed in several pathologies. Researchers suppose that altered blood levels of ncRNAs could act as a possible new diagnostic biomarker in asthma.
- Conditions
- Allergic Asthma, Severe Eosinophilic Asthma
- Being tested
- Dermatophagoides pteronyssinus allergen, Blood sampling, Bronchial challenge with allergen
- Keywords
- Eosinophils subtypes, Non-coding RNA, Exosome
- Medical subject headings
- Pulmonary Eosinophilia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dermatophagoides pteronyssinus allergenBiological
Dermatophagoides pteronyssinus allergen is required to perform allergen bronchial challenge test.
Blood samplingProcedure or surgery
An amount of a person's blood taken from their body for use in medical.
Bronchial challenge with allergenProcedure or surgery
Bronchial challenge is performed with D. pteronyssinus allergen. Measurements of differences in eosinophils activity after allergen challenge.
| Study group | Role | What they receive |
|---|---|---|
| Allergic asthma patients | Experimental | Allergic asthma patients and sensitization to house dust mites (D. pteronyssinus) allergen. Receives: Biological: Dermatophagoides pteronyssinus allergen; Procedure: Blood sampling; Procedure: Bronchial challenge with allergen |
| Severe eosinophilic asthma patients | Experimental | Not described Receives: Procedure: Blood sampling |
| Healthy subjects as a control group | Active comparator | Healthy subjects without allergic and other chronic respiratory diseases (control group). Receives: Procedure: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fold changes of ncRNA expression between eosinophils subtypes
Validated ncRNA expression of rEOS and iEOS in severe and non-severe eosinophilic asthma patients and healthy subjects.
Measured: From 6 to 12 months
ncRNA levels in rEOS- and iEOS-derived exosomes
Qualitative and quantitative selected ncRNA levels in rEOS- and iEOS-derived exosomes of all investigated groups.
Measured: From 12 to 18 months
Secondary outcomes (16)
Fold changes of ncRNA profiles of distinct eosinophil subtypes
Non-validated whole ncRNA profiles of distinct eosinophil subtypes in severe and non-severe eosinophilic asthma patients and healthy subjects.
Measured: From 6 to 12 months
The fold changes of rEOS and iEOS surface integrins expression
The gene expression of selected outer-membrane integrins in eosinophil subtypes.
Measured: From 6 to 12 months
The fold changes of rEOS and iEOS eosinophilopoietins receptors expression
The gene expression of interleukin (IL)-5, IL-3, and granulocyte-macrophage colony-stimulating factor in eosinophil subtypes.
Measured: From 6 to 12 months
The efficiency of iEOS and rEOS adhesion
The differences in stable adhered iEOS and rEOS quantity in the combined cell culture with airway smooth muscle (ASM) cells or pulmonary fibroblasts compared between the investigated groups.
Measured: From 6 to 12 months
iEOS and rEOS survival differences
Viable iEOS and rEOS number after an appropriate period of time in combined cell culture with ASM cells or pulmonary fibroblasts.
Measured: From 6 to 12 months
Quantity of iEOS and rEOS synthesized reactive oxygen species
Relative differences between iEOS and rEOS synthesized reactive oxygen species quantity after an appropriate period of incubation alone or with ASM cells or pulmonary fibroblasts.
Measured: From 6 to 12 months
Apoptotic iEOS and rEOS number
The number of apoptotic iEOS and rEOS after an appropriate period of time in combined cell culture with ASM cells or pulmonary fibroblasts.
Measured: From 6 to 12 months
Concentrations of iEOS and rEOS produced proteins in investigated subjects' body fluids.
Selected iEOS and rEOS proteins concentrations, measured in investigated subjects body fluids, expressed as the amount of protein in the respective amount of fluid sample.
Measured: From 6 to 12 months
iEOS and rEOS effect on airway smooth muscle cells or pulmonary fibroblasts proliferation
The quantity of ASM cells or pulmonary fibroblasts after several repeats of proliferation in the presence or absence of eosinophil subtypes.
Measured: From 6 to 12 months
iEOS and rEOS effect on apoptotic ASM cells and pulmonary fibroblasts number
The number of apoptotic ASM cells and pulmonary fibroblasts after an appropriate period of time in combined cell culture with iEOS and rEOS.
Measured: From 6 to 12 months
iEOS and rEOS effect on migration of ASM cells.
The migrated ASM cells number after an appropriate period of time in combined cell culture with iEOS and rEOS
Measured: From 6 to 12 months
iEOS and rEOS effect on migration of pulmonary fibroblasts
The migrated pulmonary fibroblasts number after an appropriate period of time in combined cell culture with iEOS and rEOS
Measured: From 6 to 12 months
iEOS and rEOS effect on ASM cells contractility
The relative efficiency of ASM cells' ability to contract collagen gel after an appropriate period of time in combined cell culture with iEOS and rEOS, expressed as reduced poured gel size in percentage, compared with control ASM cells without incubation with eosinophils.
Measured: From 6 to 12 months
iEOS and rEOS effect on pulmonary fibroblasts contractility
The relative efficiency of pulmonary fibroblasts ability to contract collagen gel after an appropriate period of time in combined cell culture with iEOS and rEOS. expressed as reduced poured gel size in percentage, compared with control pulmonary fibroblasts, without incubation with eosinophils.
Measured: From 6 to 12 months
iEOS and rEOS effect on fold changes of ASM cells and pulmonary fibroblasts proteins expression;
Altered selected ASM cells and pulmonary fibroblasts proteins expression, after incubation with iEOS and rEOS, expressed as fold changes in comparison with control cells, without incubation with eosinophils
Measured: From 6 to 12 months
iEOS and rEOS effect on fold changes of ASM cells and pulmonary fibroblasts proteins gene expression;
Altered selected ASM cells and pulmonary fibroblasts proteins gene expression, after incubation with iEOS and rEOS, expressed as fold changes in comparison with control cells, without incubation with eosinophils
Measured: From 6 to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start1 Oct 2020 (estimated)
- Primary completion1 Oct 2023 (estimated)
- Study completion1 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Allergic 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lithuanian University of Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kestutis Malakauskas, Lithuanian University of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04542902
- Sponsor's protocol ID
- LAB-1/2020
- Status last verified
- Aug 2020
- First submitted
- 25 Aug 2020
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Barnig C, Alsaleh G, Jung N, Dembele D, Paul N, Poirot A, Uring-Lambert B, Georgel P, de Blay F, Bahram S. Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders. PLoS One. 2015 Nov 2;10(11):e0141740. doi: 10.1371/journal.pone.0141740. eCollection 2015.
PubMed 26524763Mazzeo C, Canas JA, Zafra MP, Rojas Marco A, Fernandez-Nieto M, Sanz V, Mittelbrunn M, Izquierdo M, Baixaulli F, Sastre J, Del Pozo V. Exosome secretion by eosinophils: A possible role in asthma pathogenesis. J Allergy Clin Immunol. 2015 Jun;135(6):1603-13. doi: 10.1016/j.jaci.2014.11.026. Epub 2015 Jan 21.
PubMed 25617225Mesnil C, Raulier S, Paulissen G, Xiao X, Birrell MA, Pirottin D, Janss T, Starkl P, Ramery E, Henket M, Schleich FN, Radermecker M, Thielemans K, Gillet L, Thiry M, Belvisi MG, Louis R, Desmet C, Marichal T, Bureau F. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J Clin Invest. 2016 Sep 1;126(9):3279-95. doi: 10.1172/JCI85664. Epub 2016 Aug 22.
PubMed 27548519Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8. doi: 10.1073/pnas.0804549105. Epub 2008 Jul 28.
PubMed 18663219Perry MM, Tsitsiou E, Austin PJ, Lindsay MA, Gibeon DS, Adcock IM, Chung KF. Role of non-coding RNAs in maintaining primary airway smooth muscle cells. Respir Res. 2014 May 16;15(1):58. doi: 10.1186/1465-9921-15-58.
PubMed 24886442Rodrigo-Munoz JM, Canas JA, Sastre B, Rego N, Greif G, Rial M, Minguez P, Mahillo-Fernandez I, Fernandez-Nieto M, Mora I, Barranco P, Quirce S, Sastre J, Del Pozo V. Asthma diagnosis using integrated analysis of eosinophil microRNAs. Allergy. 2019 Mar;74(3):507-517. doi: 10.1111/all.13570. Epub 2018 Oct 11.
PubMed 30040124Zhu Y, Mao D, Gao W, Han G, Hu H. Analysis of lncRNA Expression in Patients With Eosinophilic and Neutrophilic Asthma Focusing on LNC_000127. Front Genet. 2019 Mar 19;10:141. doi: 10.3389/fgene.2019.00141. eCollection 2019.
PubMed 30941157Weller PF, Spencer LA. Functions of tissue-resident eosinophils. Nat Rev Immunol. 2017 Dec;17(12):746-760. doi: 10.1038/nri.2017.95. Epub 2017 Sep 11.
PubMed 28891557Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013 Jan;13(1):9-22. doi: 10.1038/nri3341. Epub 2012 Nov 16.
PubMed 23154224Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006;24:147-74. doi: 10.1146/annurev.immunol.24.021605.090720.
PubMed 16551246
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-coding RNAs Analysis of Eosinophil Subtypes in Asthma
- ClinicalTrials.gov ID
- NCT04542902
- Acronym / sponsor ID
- LAB-1/2020
- Conditions
- Allergic Asthma, Severe Eosinophilic Asthma
- Keywords
- Eosinophils subtypes, Non-coding RNA, Exosome
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Lithuanian University of Health SciencesUniversity, hospital or other
- Study start
- 1 Oct 2020 (estimated)
- Primary completion
- 1 Oct 2023 (estimated)
- Study completion
- 1 Oct 2023 (estimated)
- First posted
- 9 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic airway inflammation rich in eosinophils is an important feature seen in asthma. Airway and blood eosinophilia is associated with increased rates of asthma exacerbations and more intense treatment.
Recently, the existence of two distinct eosinophils subtypes was revealed-lung-resident eosinophils (rEOS), which maturate independently to interleukin (IL) 5, with the primary function to maintain tissue homeostasis, and inflammatory eosinophils (iEOS), which mature in IL-5-dependent manner and are mainly involved in immune responses. Eosinophils' effect on the airway remodeling in asthma depends not only on the activity but also by their viable number in the lungs. Blood iEOS infiltrate the airways mainly after the environmental stimulus like allergen and leave the airways with bronchial secretions. However, rEOS reside lung tissue for their entire lifetime regulating local immunity. Blood rEOS and iEOS ratio alters in asthma, compared with healthy controls. It is known that the predominant eosinophils subtype in allergic asthma are iEOS, while rEOS are basic subtype in severe eosinophilic asthma patients, moreover, they are different in adhesive properties and survivability as well. Distinct biological properties allows to speculate about their different functions in asthma, however, there are still little information. Data about differently expressed microRNA (miRNA) profiles in eosinophils in asthma suggests, that eosinophils subtypes can be distinct in non-coding RNA (ncRNA) - microRNA (miRNA), piwi-interacting RNA (piRNA) and long non-coding RNA (IncRNA) profiles that could describe their role in asthma pathogenesis and act as biomarkers to discern asthma phenotypes.
Detailed description
Asthma is not cured, and only well-balanced treatment can control the course and severity of the disease. Most clinical symptoms rise from aberrant chronic airway inflammation mostly eosinophilic. Eosinophils are terminally differentiated granulocytes that actively contribute to innate and adaptive inflammatory cascades through the production and release of diverse chemokines, cytokines, lipid mediators and other growth factors. IL-5 plays a fundamental role in eosinophils maturation in the bone marrow, their recruitment, and activation at sites of inflammation.
Historically eosinophils were described as a critical player in host defense, including parasites, viruses, fungi, or bacteria, giving them a destructive inflammatory cell label. However, it became clear that steady-state eosinophils can contribute to the immunoregulation and tissue homeostasis as well. Studies revealed that there are distinct eosinophils subtypes - immunoregulatory lung-resident eosinophils (rEOS) and inflammatory eosinophils (iEOS), involved in immune responses. Distinct eosinophils subtypes with different functions determines the separate treatment. There are still only a few studies describing distinct eosinophils subtypes in the lungs or blood. It is the beginning of a new promising research area for better individualized eosinophilic asthma treatment, moreover, other eosinophilic diseases as well.
Peripheral blood eosinophils studies are sufficiently relevant to the tissue eosinophils studies, as blood eosinophils are released into the bloodstream in a fully maturated form. Moreover, peripheral blood study could give additional information with possibilities to prevent eosinophils effects in the early stage, before migration to the airways. Furthermore, the existence of tissue-resident eosinophils in peripheral blood is confirmed and primary research for eosinophil subtypes surface markers was made according to the data of human blood eosinophils.
Data about differently differently expressed microRNA (miRNA) profiles in eosinophils in asthma suggests, that eosinophils subtypes can be distinct in non-coding RNA (ncRNA) - microRNA (miRNA), piwi-interacting RNA (piRNA) and long non-coding RNA (IncRNA) profiles that could describe their role in asthma pathogenesis and act as biomarkers to discern asthma phenotypes.
Researchers have plan to expand research by analyzing non-coding RNA (ncRNA) - miRNA, piRNA and lncRNA profiles of rEOS and iEOS as well as selected ncRNA signatures in blood plasma estimating their diagnostic value. Moreover, additional investigation of ncRNA in eosinophil-derived exosomes will provide important data about possible effect of eosinophils subtypes on airway remodeling via secreted ncRNA. ncRNAs are key regulators for gene transcription. However, there is evidence about their dysregulation in eosinophils during asthma. It will give important information about molecular signaling pathways that regulate the activity of distinct eosinophil subtypes during health and asthma, and provide the essential information about possible new therapeutic targets for their control. Additionally researchers will investigate the biological differences between rEOS and iEOS, including surface integrins and eosinophilopoietins receptors expression, adhesive properties, survivability, synthesized reactive oxygen species and apoptosis, as well as their effect on pulmonary structural cells physiological activity as proliferation, apoptosis, migration, contractility and proteins production, and will relate it with molecular signaling pathways, regulated by distinct expressed ncRNAs. ncRNAs can be stored in eosinophils exosomes and expressed to the surrounding environment. Information about ncRNAs in eosinophils-derived exosomes will demonstrate their function by affecting the other cells, especially after migration to airways. Moreover, ncRNAs are stable and resistant to blood RNases and differentially expressed in several pathologies. Researchers suppose that altered blood levels of ncRNAs could act as a possible new diagnostic biomarker in asthma.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Allergic asthma patients | Experimental | Biological: Dermatophagoides pteronyssinus allergen, Procedure: Blood sampling, Procedure: Bronchial challenge with allergenAllergic asthma patients and sensitization to house dust mites (D. pteronyssinus) allergen. |
| Severe eosinophilic asthma patients | Experimental | Procedure: Blood sampling |
| Healthy subjects as a control group | Active comparator | Procedure: Blood samplingHealthy subjects without allergic and other chronic respiratory diseases (control group). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women between the ages of 18-70 years;
- Allergic asthma and sensitization to house dust mites (D. pteronyssinus) allergen, approved with: 1) medical history and symptoms more than one year; 2) skin prick test positive for D. pteronyssinus (positive wheals are those exceeding 3 mm in diameter greater than the negative control); 3) positive bronchial challenge with methacholine or documented reversible bronchial obstruction;
- Severe eosinophilic asthma;
- Premenopausal women if pregnancy test is negative;
- Healthy subjects without allergic and other chronic respiratory diseases (control group);
Key exclusion criteria (8 listed)
- Asthma exacerbation 1 month prior to study;
- Clinically significant permanent allergy symptoms (ex. cat or dog dander induced allergy);
- Contraindications to perform an allergy skin test and/or bronchial provocation test: 1) active airway infection 1 month prior the study; 2) used medicaments: inhaled glucocorticoids intake 1 month prior the study, antihistamines intake 7 days prior the study; 3) short acting β2 agonists 12 hours prior the study; 4) long acting β2 agonists 2 days prior the study; 5) leukotriene receptor antagonists prior 14 days;
- Contraindications for epinephrine;
- Other significant mental and / or internal diseases and conditions, which could be as exclusion criteria due to the opinion of the researcher;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dermatophagoides pteronyssinus allergenDermatophagoides pteronyssinus allergen is required to perform allergen bronchial challenge test. | Biological | Allergic asthma patients |
| Blood samplingAn amount of a person's blood taken from their body for use in medical. | Procedure or surgery | Allergic asthma patients, Healthy subjects as a control group, Severe eosinophilic asthma patients |
| Bronchial challenge with allergenBronchial challenge is performed with D. pteronyssinus allergen. Measurements of differences in eosinophils activity after allergen challenge. | Procedure or surgery | Allergic asthma patients |
Primary outcome
Fold changes of ncRNA expression between eosinophils subtypes
Time frame: From 6 to 12 months
Validated ncRNA expression of rEOS and iEOS in severe and non-severe eosinophilic asthma patients and healthy subjects.
ncRNA levels in rEOS- and iEOS-derived exosomes
Time frame: From 12 to 18 months
Qualitative and quantitative selected ncRNA levels in rEOS- and iEOS-derived exosomes of all investigated groups.
16 secondary outcomes
Fold changes of ncRNA profiles of distinct eosinophil subtypes
Time frame: From 6 to 12 months
The fold changes of rEOS and iEOS surface integrins expression
Time frame: From 6 to 12 months
The fold changes of rEOS and iEOS eosinophilopoietins receptors expression
Time frame: From 6 to 12 months
The efficiency of iEOS and rEOS adhesion
Time frame: From 6 to 12 months
iEOS and rEOS survival differences
Time frame: From 6 to 12 months
Quantity of iEOS and rEOS synthesized reactive oxygen species
Time frame: From 6 to 12 months
Apoptotic iEOS and rEOS number
Time frame: From 6 to 12 months
Concentrations of iEOS and rEOS produced proteins in investigated subjects' body fluids.
Time frame: From 6 to 12 months
iEOS and rEOS effect on airway smooth muscle cells or pulmonary fibroblasts proliferation
Time frame: From 6 to 12 months
iEOS and rEOS effect on apoptotic ASM cells and pulmonary fibroblasts number
Time frame: From 6 to 12 months
iEOS and rEOS effect on migration of ASM cells.
Time frame: From 6 to 12 months
iEOS and rEOS effect on migration of pulmonary fibroblasts
Time frame: From 6 to 12 months
iEOS and rEOS effect on ASM cells contractility
Time frame: From 6 to 12 months
iEOS and rEOS effect on pulmonary fibroblasts contractility
Time frame: From 6 to 12 months
iEOS and rEOS effect on fold changes of ASM cells and pulmonary fibroblasts proteins expression;
Time frame: From 6 to 12 months
iEOS and rEOS effect on fold changes of ASM cells and pulmonary fibroblasts proteins gene expression;
Time frame: From 6 to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Background: PubMed 26524763Barnig C, Alsaleh G, Jung N, Dembele D, Paul N, Poirot A, Uring-Lambert B, Georgel P, de Blay F, Bahram S. Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders. PLoS One. 2015 Nov 2;10(11):e0141740. doi: 10.1371/journal.pone.0141740. eCollection 2015.
- Background: PubMed 25617225Mazzeo C, Canas JA, Zafra MP, Rojas Marco A, Fernandez-Nieto M, Sanz V, Mittelbrunn M, Izquierdo M, Baixaulli F, Sastre J, Del Pozo V. Exosome secretion by eosinophils: A possible role in asthma pathogenesis. J Allergy Clin Immunol. 2015 Jun;135(6):1603-13. doi: 10.1016/j.jaci.2014.11.026. Epub 2015 Jan 21.
- Background: PubMed 27548519Mesnil C, Raulier S, Paulissen G, Xiao X, Birrell MA, Pirottin D, Janss T, Starkl P, Ramery E, Henket M, Schleich FN, Radermecker M, Thielemans K, Gillet L, Thiry M, Belvisi MG, Louis R, Desmet C, Marichal T, Bureau F. Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J Clin Invest. 2016 Sep 1;126(9):3279-95. doi: 10.1172/JCI85664. Epub 2016 Aug 22.
- Background: PubMed 18663219Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8. doi: 10.1073/pnas.0804549105. Epub 2008 Jul 28.
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- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dermatophagoides pteronyssinus allergen, Blood sampling and Bronchial challenge with allergen in people with Allergic Asthma and Severe Eosinophilic Asthma, run by Lithuanian University of Health Sciences at 1 site in Lithuania.
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 6 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 9 Sep 2020. 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 Lithuania. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kestutis Prof. Dr. Malakauskas (+37037326737, kestutis.malakauskas@lsmuni.lt), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fold changes of ncRNA expression between eosinophils subtypes (time frame: From 6 to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04542902, which also lists 10 linked publications.
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 9 Sep 2020.