Genomics and Metagenomics of Asthma Severity (GEMAS)

• ClinicalTrials.gov Identifier: NCT04501926
• Recruitment Status: Unknown
• First Posted: August 6, 2020
• Last Update Posted: May 17, 2022
• Sponsor: Maria Pino-Yanes
• Collaborators: University of La Laguna; Spanish Ministry of Science, Innovation, and Universities; Consorcio Centro de Investigación Biomédica en Red (CIBER); University Hospital of the Nuestra Señora de Candelaria; Hospital Universitario de Canarias; Hospital General de La Palma; Hospital Universitario Donostia; Hospital Doctor Jose Molina Orosa
• Information provided by (Responsible Party): Maria Pino-Yanes, University of La Laguna

Tracking Information

• First Submitted Date: July 30, 2020
• First Posted Date: August 6, 2020
• Last Update Posted Date: May 17, 2022
• Actual Study Start Date: March 1, 2018
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 3, 2020)

Severe asthma exacerbations [ Time Frame: 1 year ]

Defined by one of the following events because of asthma during the past year, the past 6 months, and the past week: oral corticosteroids use, emergency room visit, and/or hospitalizations

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 3, 2020)

• Asthma control [ Time Frame: 1 week ]
  Asthma control questionnaire (ACQ) score
• Asthma severity [ Time Frame: 1 year ]
  Category of severity defined by treatment step according to GINA 2020 at recruitment
• Lung function measurement: forced expiratory volume in the first second (FEV1) [ Time Frame: 3 months ]
  Baseline and post-bronchodilator measurements of the forced expiratory volume in the first second (FEV1) measured in liters
• Lung function measurement: forced vital capacity (FVC) [ Time Frame: 3 months ]
  Baseline and post-bronchodilator measurements of the forced vital capacity (FVC) measured in liters
• Lung function measurement: FEV1/FVC ratio [ Time Frame: 3 months ]
  The ratio of FEV1/FVC measurements
• Atopy testing [ Time Frame: 1 year ]
  Atopy status evaluated by skin prick tests and/or specific immunoglobulin E (IgE) levels assessing the most common aeroallergens of each recruiting center

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Genomics and Metagenomics of Asthma Severity
• Official Title: Genomics and Metagenomics of Asthma Severity
• Brief Summary: The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of genomics, the microbiome, and the interaction between them in the development of asthma exacerbations in European patients with asthma.

Detailed Description

Asthma is a chronic inflammatory disease of the airways characterized by reversible airflow obstruction and a bronchial hyperreactivity in response to a variety of stimuli. In most patients, the onset of asthma symptoms may be controlled. However, many of them may manifest asthma attacks or crises of breathing called exacerbations, which occur with breathing problems, wheezing, coughing or tightness of chest, and may threaten their life. Such exacerbations are caused by a combination of environmental and genetic factors. However, since studies so far have been limited, a reduced number of genes associated with the predisposition to these complications have been identified. In addition, some studies have used next-generation DNA sequencing techniques to characterize the microbiome (i.e., microbial community) of the airways, finding changes related to asthma. The main hypothesis of the Genomics and Metagenomics of Asthma Severity (GEMAS) study is that exacerbations of asthma are caused by a combination of the intrinsic genetic factors of the individual, changes in the respiratory microbiome and the interaction between both factors. The objectives of this project are: 1) to identify genetic variants that are associated with asthma exacerbations; 2) to examine the changes occurring in the microbial communities of the oral cavity and respiratory tract in individuals with exacerbations; 3) to analyze the association of the host genetic variants and the microbiome changes related to exacerbations.

A total of 300 Spanish subjects with asthma with and without a history of asthma exacerbations in the past 12 months will be recruited. Saliva, nasal and pharyngeal samples will be collected to study the oral cavity and the upper respiratory tract microbiome through next-generation sequencing technologies. Sequencing of the 16S ribosomal RNA (16S rRNA) gene will allow to characterize the bacterial diversity and abundance, as well as to infer the functionality of the microbiome in each sample. These parameters will be used to establish correlations between the microbiome and the presence of asthma exacerbations. Finally, the association between the genetic variation associated with exacerbations in genomic studies and the measurements of abundance, diversity and functions related to exacerbations will be jointly examined.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Blood samples are drown in EDTA tubes and PAXGene tubes for human DNA and RNA extraction, respectively. For the human microbiome study, saliva samples and nasal and pharyngeal swaps are collected.

• Sampling Method: Probability Sample
• Study Population: Patients are recruited from the allergy and/or pulmonary medicine units from hospitals located in the Canary Islands, Spain (Hospital Universitario de Canarias, Hospital Universitario Nuestra Señora de Candelaria, Hospital General de La Palma, and Hospital Doctor Jose Molina Orosa), and in the division of pediatric respiratory medicine of Hospital Universitario Donostia in the Basque Country, Spain.

Condition

• Asthma
• Asthma Attack

• Intervention: Not Provided

Study Groups/Cohorts

• Controls
  Asthma patients who did not report asthma exacerbations in the 12 months prior recruitment, defined by one of the following events because of asthma: oral corticosteroids use, emergency room visits, and/or hospitalizations.
• Cases
  Asthma patients that reported asthma exacerbations in the 12 months prior recruitment, defined by one of the following events because of asthma: oral corticosteroids use, emergency room visits, and/or hospitalizations.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 3, 2020): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female aged older or equal than 8 years and younger or equal than 85 years
• Physician diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines
• Treated on GINA step 1-5

Exclusion Criteria:

• One or more grandparents of non-European origin
• Pregnancy
• Coexistence of other chronic pulmonary disorders including cystic fibrosis, chronic obstructive pulmonary disease (emphysema or chronic bronchitis), or congenital disorders of the lungs or airways
• Known family relatedness (first or second degree) with another participant already included in the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 8 Years to 85 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT04501926
• Other Study ID Numbers: PI-29/17
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Maria Pino-Yanes, University of La Laguna
• Original Responsible Party: Same as current
• Current Study Sponsor: Maria Pino-Yanes
• Original Study Sponsor: Same as current

Collaborators

• University of La Laguna
• Spanish Ministry of Science, Innovation, and Universities
• Consorcio Centro de Investigación Biomédica en Red (CIBER)
• University Hospital of the Nuestra Señora de Candelaria
• Hospital Universitario de Canarias
• Hospital General de La Palma
• Hospital Universitario Donostia
• Hospital Doctor Jose Molina Orosa

• Investigators: Not Provided
• PRS Account: University of La Laguna
• Verification Date: May 2022