Epigenetic Regulation of Exercise Induced Asthma

House Dust Mite Allergy Clinical Trial

Official title:

Epigenetic Regulation of Excercise Induced Asthma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05174689
• Other study ID #: E68/21
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2021
• Est. completion date: September 2022

Study information

• Verified date: December 2021
• Source: Johann Wolfgang Goethe University Hospital
• Contact: Melanie Dreßler, MD
• Phone: +49-69-6301-4588
• Email: melanie.dressler[@]kgu.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the micro ribonucleic acid (mRNA) profiles of patients with EIA without allergic sensitization and EIA with house dust mite sensitization compared to that of healthy controls.

Description:

Patients with known EIA are periodically reexamined by medical history, clinical examination, bodyplethysmography, spirometry, exhaled nitric oxide (eNO), skin prick test, methacholin challenge test and exercise-challenge in a cold-chamber at 2-4°C (ECC). Additionally the investigators gathers the questionnaires: Asthma Control Test (ACT) and Dyspnoe Index (DI).

Besides these standard procedures the investigators want to investigate the micro-RNA profiles in two EIA subgroups: EIA with house-dust allergy (n = 24) and EIA without house-dust allergy (n = 24).

Both groups are characterized by different eNO levels. The patients with EIA and house-dust allergy should have an eNO > 30 ppb, the patients with EIA without house-dust allergy an eNO < 20 ppb.

The micro-RNA profiles of the both EIA subgroups will be compared the micro RNA profiles of 20 healthy controls .

Therefore blood will be taken (for a complete blood count and micro RNA analysis) at three points of time: before ECC, directly after ECC and after 24 hours ± 4 hours after ECC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: September 2022
• Est. primary completion date: August 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 24 Years

Eligibility

For EIA patients

Inclusion Criteria:

• written agreement

• age >=12 and <= 24

• known exercise induced asthma

• Group 1: skin prick test positiv house-dust allergy, eNO > 30 ppb, MCT PD20 < 0,1 mg

• Group 2: skin prick test negative house-dust allergy, eNO < 20 ppb, MCT PD20 < 1 mg

• lung function before ECC forced vital capacity (FVC) = 75% and forced exspiratory pressure in one second (FEV1) = 70%

Exclusion Criteria:

• age < 12 und > 24 years

• lung function FVC < 75% und FEV1< 70%

• inability to understand the range of the study

• chronic asthma with systemic cortisone therapy

• regular therapy with inhalative corticosteroids or leukotriene-antagonists <14 days before visit 1

• intake of long acting beta-agonists (LABA) 48 h before examination

• intake of short acting beta-agonists (SABA) 8 h before examination

• acute severe infection (pneumonia) within the last 4 weeks

• other chronic diseases or infections (HIV, Tbc)

• pregnancy

For healthy controls

Inclusion Criteria:

• written agreement

• age >=18 and <= 24

Exclusion Criteria:

• age < 18 and > 24 years

• known asthma bronchiale or other chronic lung diseases

• lung function FVC < 90% and FEV1 < 80%

• allergic sensitization in skin prick test

• eNO > 30 ppb

• inability to understand the range of the study

• acute severe infection (pneumonia) within the last 4 weeks

• other chronic diseases or infections (HIV, Tbc)

• pregnancy

Related Conditions & MeSH terms

• Asthma
• Asthma, Exercise-Induced
• Exercise Induced Asthma
• House Dust Mite Allergy

Intervention

Diagnostic Test:
• Exercise challenge in the cold chamber (ECC)
Exercise challenge (defined as running on a treadmill for 6-8 minutes on submaximal work load in a cold chamber. Gradient: 10%, temperature 2-4°C. After the exercise challenge controlling bodyplethysmography and spirometry after 5, 10, 15 and 30 minutes. A positive reaction is a decrease of = 10% of FEV1 in comparison to the initial value.
• mRNA profile
Blood taking with full blood exam and PAXgene tube for investigation oft the micro RNA profiles. The PAXgene Blood RNA kit insulates total RNA inclusive miRNA and small RNA which are centrifugated, pelletised, washed and incubated to detach proteins. For mapping the particular miRNA there will be generated libraries with specifical codes to match the analysis to the original probe. Next generation sequencing will be performed by MISeq REagent Kit v3 and the analysis oft the different expressions in the R Version 3.2.3. The divergent expressions will be refurbished by computer and databased.
• standard diagnostic
bodyplethysmography, spirometry, exhaled NO, skin prick test, asthma control test (ACT)

Locations

Country	Name	City	State
Germany	Universitätsklinikum Frankfurt	Frankfurt	Hessen

Sponsors (1)

Lead Sponsor	Collaborator
Johann Wolfgang Goethe University Hospital

Country where clinical trial is conducted

Germany, 

References & Publications (27)

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Dreßler M, Salzmann-Manrique E, Zielen S, Schulze J. Exhaled NO as a predictor of exercise-induced asthma in cold air. Nitric Oxide. 2018 Jun 1;76:45-52. doi: 10.1016/j.niox.2018.03.004. Epub 2018 Mar 8. — View Citation

Driessen JM, van der Palen J, van Aalderen WM, de Jongh FH, Thio BJ. Inspiratory airflow limitation after exercise challenge in cold air in asthmatic children. Respir Med. 2012 Oct;106(10):1362-8. doi: 10.1016/j.rmed.2012.06.017. Epub 2012 Jul 11. — View Citation

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Fussbroich D, Kohnle C, Schwenger T, Driessler C, Dücker RP, Eickmeier O, Gottwald G, Jerkic SP, Zielen S, Kreyenberg H, Beermann C, Chiocchetti AG, Schubert R. A combination of LCPUFAs regulates the expression of miRNA-146a-5p in a murine asthma model and human alveolar cells. Prostaglandins Other Lipid Mediat. 2020 Apr;147:106378. doi: 10.1016/j.prostaglandins.2019.106378. Epub 2019 Nov 4. — View Citation

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Jerkic SP, Michel F, Donath H, Herrmann E, Schubert R, Rosewich M, Zielen S. Calprotectin as a New Sensitive Marker of Neutrophilic Inflammation in Patients with Bronchiolitis Obliterans. Mediators Inflamm. 2020 May 1;2020:4641585. doi: 10.1155/2020/4641585. eCollection 2020. — View Citation

Kumar M, Mabalirajan U, Agrawal A, Ghosh B. Proinflammatory role of let-7 miRNAs in experimental asthma? J Biol Chem. 2010 Nov 26;285(48):le19: author reply le20. doi: 10.1074/jbc.L110.145698. — View Citation

Liu X, Nelson A, Wang X, Kanaji N, Kim M, Sato T, Nakanishi M, Li Y, Sun J, Michalski J, Patil A, Basma H, Rennard SI. MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis. Biochem Biophys Res Commun. 2009 Feb 27;380(1):177-82. doi: 10.1016/j.bbrc.2009.01.066. Epub 2009 Jan 22. — View Citation

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Rosewich M, Zissler UM, Kheiri T, Voss S, Eickmeier O, Schulze J, Herrmann E, Dücker RP, Schubert R, Zielen S. Airway inflammation in children and adolescents with bronchiolitis obliterans. Cytokine. 2015 May;73(1):156-62. doi: 10.1016/j.cyto.2014.10.026. Epub 2015 Mar 6. — View Citation

Schulze J, Rosewich M, Dressler M, Riemer C, Rose MA, Zielen S. Bronchial allergen challenge using the Medicaid dosimeter. Int Arch Allergy Immunol. 2012;157(1):89-97. doi: 10.1159/000324473. Epub 2011 Sep 7. — View Citation

Schulze J, Rosewich M, Riemer C, Dressler M, Rose MA, Zielen S. Methacholine challenge--comparison of an ATS protocol to a new rapid single concentration technique. Respir Med. 2009 Dec;103(12):1898-903. doi: 10.1016/j.rmed.2009.06.007. Epub 2009 Jul 10. — View Citation

Schulze J, Smith HJ, Fuchs J, Herrmann E, Dressler M, Rose MA, Zielen S. Methacholine challenge in young children as evaluated by spirometry and impulse oscillometry. Respir Med. 2012 May;106(5):627-34. doi: 10.1016/j.rmed.2012.01.007. Epub 2012 Feb 10. — View Citation

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dysregulation of miRNA-146	The primary endpoint is the dysregulation of miRNA-146 in comparison to the control group and within the subgroups which play an determined role in the bronchial inflammation.; Therefore the total RNA, including miRNA, will be isolated using the PAXgene Blood miRNA Kit (Qiagen, Hilden, Germany). Concentration of RNA will be assessed using Nanodrop Lite spectrometry (Thermo Scientific, Dreieich, Germany). MiRNA libraries are generated with the QIAseq miRNA Library Kit (Qiagen, Hilden, Germany). Next generation sequencing (NGS) will be performed with the MiSeq Reagent Kit v3, the PhiX Sequencing Control v3 and the MiSeq™ Desktop Sequencer (all Illumina Inc., San Diego, CA, USA). Differential expression analysis will be performed in RStudio 1.2.1335 (https://cran.r-project.org/). False discovery rate correction will be applied and miRNAs are considered to be differentially expressed with p < 0.05.	1 Year
Secondary	Dysregulation miRNAs affecting Th2 mediated bronchial inflammation (miRNA-126, miRNA-21, miRNA-145, let7-mimic)	Dysregulation of other miRNAs affecting the Th2 mediated bronchial inflammation (miRNA-126, miRNA-21, miRNA-145, let7-mimic) and compare to the control group.; MiRNA preparation and measurement processes are described in Outcome 1.	1 Year
Secondary	Cange of eNO	Change of eNO after ECC in the EIA subgroups compared to the healthy controls	1 Year
Secondary	Change of leucocytes and neutrophile granulocytes	Change of leucocytes and neutrophile granulocytes after ECC in the EIA subgroups compared to the healthy controls	1 Year
Secondary	FEV1-decrease in ECC	Comparison of the FEV1-decrease in ECC with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls	1 Year
Secondary	Comparison eNO with significant dysregulated miRNA	Comparison of the initial value of exhaled NO with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls	1 Year
Secondary	Comparison of change of leucocytes and neutrophile granulocytes with significant dysregulated miRNA	Comparison of the increase of leucocytes and neutrophile granulocytes after ECC significant dysregulated miRNA in the EIA subgroups compared to the healthy controls	1 Year
Secondary	Comparison of ACT with significant dysregulated miRNA	Comparison of the score in ACT with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls	1 Year
Secondary	Comparison of DI with significant dysregulated miRNA	Comparison of the scoresin DI with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls	1 Year