Asthma Origins and Remission Study (ARMS)

July 12, 2017 updated by: Maarten van den Berge, University Medical Center Groningen

A Better Understanding of Molecular Mechanisms Leading to Asthma and Its Remission

Asthma is characterized by chronic airway inflammation of the large and small airways. Asthma patients often have episodes with symptoms of dyspnea, wheezing and nocturnal awakening. Currently available inhaled anti-inflammatory treatments reduce the airway inflammation and treatment but do not cure the disease. Therefore asthma patients often need life-long treatment to control their asthma.

In a small subset of patients, their asthma resolves spontaneously. This phenomenon is called asthma remission. Subjects with asthma remission do not experience symptoms or signs of airway inflammation anymore and do not require inhaled treatments. Some subjects with asthma remission also have a completely normal lung function without signs of bronchial hyperresponsivess: they have complete asthma remission. Unfortunately, asthma remission occurs only in a small subset of 15-25% of asthma patients.Objective: to determine the underlying mechanisms and molecular events leading to remission of asthma.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Rationale: Asthma inception occurs only in susceptible individuals, and is often triggered by specific environmental factors, such as respiratory viruses and aeroallergens. Although asthma is generally viewed as a chronic persistent disease, remission of asthma is possible in a subset of patients. This is highly relevant, since understanding mechanisms that contribute to asthma inception and remission may teach us how asthma can be stopped and thus may provide novel avenues for the treatment of asthma. In adulthood, average remission rates of asthma are approximate 2% per year 1. We observed that remission in adulthood is more likely with earlier onset of asthma, less airway obstruction, more severe bronchial hyperresponsiveness, and smoking cessation. A proper definition of remission is very important; we therefore introduced the terms 'clinical remission' and 'complete remission' 2. Clinical remission was defined as the absence of asthma symptoms and no use of asthma medication, complete remission as the absence of asthma symptoms, no use of asthma medication, normal lung function and no bronchial hyperresponsiveness. In a longitudinal study of 119 allergic asthmatic children followed-up for 30 years, our group found that clinical remission occurred in 30% and complete remission in 22% of all cases.

Objective: to determine the underlying mechanisms and molecular events involved in the inception and remission of asthma.

Methods: We will include a 40 subjects divided over the following 4 groups: i) clinical asthma remission (10 subjects), ii) complete asthma remission (10 subjects), iii) ongoing asthma (10 patients), iv) non-asthmatic healthy controls (10 subjects) in a cross-sectional study. All subjects will be extensively clinically characterized including respiratory symptoms/questionnaires, in- and expiratory CT-scans, and parameters of large and small airway function and inflammation. In addition, blood and nasal epithelial brushes will be obtained to study the genetic and epigenetic mechanisms of asthma remission. Finally, bronchoscopy with bronchial biopsies and brushes will be performed under conscious sedation. Bronchial biopsies from all four patient groups will be used for index FACS sorting of the three most important cell types orchestrating the asthmatic inflammatory process: i.e. B lymphocytes, CD4+ T cells and CD8+ T cells. We will perform single cell whole-genome transcriptome sequencing on at least 100 cells of each type and the primary outcome of the study is to identify how the transcriptomic profile of bronchial epithelial cells is changed between asthma patients and healthy controls as a consequence of asthma inception and what transcriptomic profile changes occur in CD4+ CD8+ and B lymphocytes in the airways from subjects with asthma remission compared to patients with ongoing asthma and healthy controls.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Martijn Nawijn, PhD
  • Phone Number: +31-50-3610998
  • Email: m.nawijn@umcg.nl

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

  • 20 patients with a documented history of asthma who have clinical asthma remission.
  • 20 patients with a documented history of asthma who have complete asthma remission.
  • 20 patients with current asthma.
  • 20 healthy subjects.

Description

Inclusion criteria for all subjects:

  • Age between 40 and 65 years old.
  • Smoking history ≤ 10 packyears.

Inclusion criteria for all asthmatics and asthma remission subjects:

• Development of asthma symptoms before 21 years.

Specific inclusion criteria for the 4 different groups:

  • Group 1. Subjects with clinical asthma remission:

    • Documented history of asthma diagnosed according to latest GINA guidelines, i.e. respiratory symptoms and either bronchodilator reversibility (improvement in FEV1 of more than 12% of baseline (and at least 200 mL) after inhalation of 800 µg salbutamol.
    • No use of asthma medications such as inhaled or oral corticosteroids, β2-agonists or anticholinergic in the last 3 years.
    • No symptoms of wheeze or asthma attacks during the last 3 years.

  • Group 2. Subjects with complete asthma remission

    • Documented history of asthma diagnosed according to latest GINA guidelines, i.e. respiratory symptoms and either bronchodilator reversibility (improvement in FEV1 of more than 12% of baseline (and at least 200 mL) after inhalation of 800 µg salbutamol.
    • No use of asthma medications such as inhaled or oral corticosteroids, β2-agonists or anticholinergics in the last 3 years.
    • No symptoms of wheeze or asthma attacks during the last 3 years.
    • FEV1 > 90% predicted.
    • Absence of bronchial hyperresponsiveness, i.e. both PC20 methacholine > 8 mg/ml and PC20 AMP > 320 mg/ml.

  • Group 3. Patients with ongoing asthma

    • Documented history of asthma diagnosed according to latest GINA guidelines, i.e. respiratory symptoms and either bronchodilator reversibility (improvement in FEV1 of more than 12% of baseline (and at least 200 mL) after inhalation of 800 µg salbutamol.
    • Use of inhaled corticosteroids or either persistent symptoms of wheeze, cough, or dyspnea or regular use of β2 agonists at least once a week during the last 2 months.
    • PC20 methacholine < 8 mg/ml.

  • Group 4. Non-asthmatic controls

    • No history of asthma.
    • No use of inhaled corticosteroids or β2-agonists for a period longer than 1 month.
    • No symptoms of wheeze, nocturnal dyspnea, or bronchial hyperresponsiveness.
    • PC20 methacholine > 8 mg/ml, FEV1/FVC > 70% and FEV1 > 80% predicted.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
asthma
20 patients with ongoing ashma
complete asthma remission
20 subjects with complete asthma remission
clinical asthma remission
20 subjects with clinical asthma remission
non-asthmatic healthy controls
20 subjects without respiratory symptoms and normal lung function and no bronchial hyperresponsiveness to methacholine and/or AMP

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Single cell sequencing data
Time Frame: baseline
Single cell mRNA sequencing of lymphocytes in bronchial biopsies and blood eosinophils
baseline

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Spirometry
Time Frame: baseline
FEV1, FVC, FEV1/FVC, FEF25-75.
baseline
body box
Time Frame: baseline
RV, RV/TLC, FRC, IC, ERV
baseline
HRCT
Time Frame: baseline
emphysema and small airways disease
baseline
Airway inflammation
Time Frame: baseline
Sputum, blood, biopsy inflammatory cell counts, exhaled nitric oxide, small particles in exhaled breath
baseline
Small airways disease
Time Frame: baseline
Multiple breath nitrogen washout: LCI, Sacin, Scond
baseline
genetic and genome-wide mRNA, non-coding RNA, and DNA methylation
Time Frame: baseline
assessed in bronchial and nasal epithelial brushes, biopsies and blood
baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Medical Center Groningen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GlaxoSmithKline

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Maarten van den Berge, MD PhD, University Medical Center Groningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2015

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 3, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 5, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 17, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 12, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL2015001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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