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Epigenetic Regulation of Exercise Induced Asthma

Sponsor
Johann Wolfgang Goethe University Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05174689
Collaborator
(none)
68
Enrollment
1
Location
3
Arms
13
Anticipated Duration (Months)
5.2
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Diagnostic Test: Exercise challenge in the cold chamber (ECC)
  • Diagnostic Test: mRNA profile
  • Diagnostic Test: standard diagnostic
 N/A

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
68 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The micro RNA profile of patients with known EIA and house dust mite allergy and patients with EIA without allergic sensitization are compared to the micro RNA profile of healthy controlsThe micro RNA profile of patients with known EIA and house dust mite allergy and patients with EIA without allergic sensitization are compared to the micro RNA profile of healthy controls
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Epigenetic Regulation of Excercise Induced Asthma
Actual Study Start Date :
Aug 1, 2021
Anticipated Primary Completion Date :
Aug 1, 2022
Anticipated Study Completion Date :
Sep 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Other: EIA wih house dust mite

Patients with EIA and house-dust mite allergy and an eNO > 30 ppb

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.

Diagnostic Test: 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.

Diagnostic Test: standard diagnostic
bodyplethysmography, spirometry, exhaled NO, skin prick test, asthma control test (ACT)
Other: EIA without sensitization

Patients with EIA without allergic sensitization and an eNO < 20 ppb

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.

Diagnostic Test: 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.

Diagnostic Test: standard diagnostic
bodyplethysmography, spirometry, exhaled NO, skin prick test, asthma control test (ACT)
Other: Healthy controls

Healthy controls without allergic sensitization or known asthma

Diagnostic Test: 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.

Diagnostic Test: standard diagnostic
bodyplethysmography, spirometry, exhaled NO, skin prick test, asthma control test (ACT)

Outcome Measures

Primary Outcome Measures

  1. Dysregulation of miRNA-146 [1 Year]

    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.

Secondary Outcome Measures

  1. Dysregulation miRNAs affecting Th2 mediated bronchial inflammation (miRNA-126, miRNA-21, miRNA-145, let7-mimic) [1 Year]

    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.

  2. Cange of eNO [1 Year]

    Change of eNO after ECC in the EIA subgroups compared to the healthy controls

  3. Change of leucocytes and neutrophile granulocytes [1 Year]

    Change of leucocytes and neutrophile granulocytes after ECC in the EIA subgroups compared to the healthy controls

  4. FEV1-decrease in ECC [1 Year]

    Comparison of the FEV1-decrease in ECC with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls

  5. Comparison eNO with significant dysregulated miRNA [1 Year]

    Comparison of the initial value of exhaled NO with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls

  6. Comparison of change of leucocytes and neutrophile granulocytes with significant dysregulated miRNA [1 Year]

    Comparison of the increase of leucocytes and neutrophile granulocytes after ECC significant dysregulated miRNA in the EIA subgroups compared to the healthy controls

  7. Comparison of ACT with significant dysregulated miRNA [1 Year]

    Comparison of the score in ACT with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls

  8. Comparison of DI with significant dysregulated miRNA [1 Year]

    Comparison of the scoresin DI with significant dysregulated miRNA in the EIA subgroups compared to the healthy controls

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years to 24 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Universitätsklinikum Frankfurt Frankfurt Hessen Germany 60590

Sponsors and Collaborators

  • Johann Wolfgang Goethe University Hospital

Investigators

  • Principal Investigator: Melanie Dreßler, MD, Johann Wolfgang Goethe University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Stefan Zielen, Prof. Dr. med., Johann Wolfgang Goethe University Hospital
ClinicalTrials.gov Identifier:
NCT05174689
Other Study ID Numbers:
  • E68/21
First Posted:
Jan 3, 2022
Last Update Posted:
Jan 3, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Stefan Zielen, Prof. Dr. med., Johann Wolfgang Goethe University Hospital
Exercise Induced Asthma
eNO
exercise challenge
micro RNAs
Additional relevant MeSH terms:
Asthma
Asthma, Exercise-Induced

Study Results

No Results Posted as of Jan 3, 2022