Clinical trial NCT04748055: Examining Changes in Nasal IL-1 During Acute Asthma Exacerbation in Adolescents
Official title: A Pilot Study Examining Changes in Nasal IL-1 During Acute Asthma Exacerbation in Adolescents
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Keywords: Asthma in children
Asthma attack
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-02-10
Enrollment: 40
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study team will recruit 60 teens and young adults with persistent asthma who are at high risk for future exacerbation from the UNC Children's Allergy and Asthma Center in Raleigh, NC.

Brief summary: To study the change from baseline in IL-1β (interleukin 1 beta) concentrations in the nasal airway during acute asthma exacerbation, specifically to measure the degree of change and identify the timing of peak IL-1β concentration. This information will allow the investigators to estimate effect size and guide decisions about the optimal timing of anakinra administration for the future study.

Detailed description: The study team will recruit 60 teens and young adults with persistent asthma who are at high risk for future exacerbation from the University of North Carolina at Chapel Hill (UNC) Children's Allergy and Asthma Center in Raleigh, NC. Participants will complete 13 study visits: an initial in-person visit (the study team will make every attempt to coordinate this visit with a scheduled clinic visit) and 12 monthly virtual follow up visits. Participants will be asked to use an at home spirometer once daily in the evening and will also complete an electronic asthma survey each night. Participants will also be provided with a sensor that tracks their rescue medication use throughout the study. Participants will undergo collection of nasal epithelial lining fluid (NELF) at the baseline visit. During the 12 months of study, participants will self-collect NELF samples if certain prespecified criteria for asthma exacerbation are met. Samples will be analyzed for IL-1β, interleukin receptor antagonist (IL-1RA) and other mediators associated with acute asthma exacerbation. Virtual follow up visits using a video platform will occur monthly for 12 months. Participants will self-report healthcare utilization and prescription for systemic corticosteroids. Spirometry and symptom survey data will be matched to subject-reported asthma exacerbations. The study design is adapted to minimize in-person visits, using web-based platforms for virtual visits and self-collection of samples to prioritize safety during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.

Eligibility criteria: Inclusion Criteria:

* Ages 12 to 21 years, inclusive, of both genders
* Physician diagnosis of persistent asthma or symptoms consistent with persistent asthma based on expert guidelines for diagnosis and management of asthma (1).
* Current use of a controller therapy such as an inhaled corticosteroid (ICS), ICS in combination with long-acting beta agonist (LABA), or leukotriene receptor antagonist (LTRA).
* Asthma is "not well controlled" (participant must have ≥1 of the following):

  * Asthma Control Test (ACT) score \<20,
  * FEV1 \<80% of predicted,
  * Meets Global Initiative on Asthma (GINA) criteria for partly controlled or uncontrolled asthma (2):

In the past 4 weeks, has the patient had:

* Daytime symptoms \>2x/week?
* Any night waking due to asthma?
* SABA reliever needed \>2x/week?
* Any activity limitation due to asthma?

  * \[0 = Well controlled; 1-2 = Partly controlled; 3-4 = Uncontrolled\]
  * A history of at least one exacerbation requiring systemic corticosteroids (oral, IM or IV) in the past 24 months

    * Access to a smartphone
    * Wireless internet access in the participant's home
    * Access to a standard freezer in the home

Exclusion Criteria:

* Systemic corticosteroid-dependent asthma (i.e. people who take oral steroids such as prednisone daily for asthma control). Use of other immunomodulator medications (such as biologics for asthma like omalizumab, etc) is allowable so long as the participant has been on a stable dose of the medication for at least 3 months.
* Participants whose asthma is sufficiently severe that the participants routinely require rescue albuterol multiple times a day for symptom relief (not including pre-exercise albuterol use).
* Pulmonary disease other than asthma that in the opinion of investigators may affect the interpretation of spirometry data, including but not limited to vocal cord dysfunction, restrictive lung disease, or cystic fibrosis.
* Inability to perform spirometry.
* History of spirometry-induced bronchoconstriction.
* Pregnancy or nursing a baby. Due to the effect of hormonal changes of pregnancy/lactation on airway inflammation, participants who are pregnant or nursing will be excluded from study.

Primary outcomes:
measure: Change from baseline in Nasal IL-1β (pg/mL) Concentrations over time during Asthma Exacerbation
timeFrame: Baseline and up to 5 days from the time asthma exacerbation is diagnosed
Secondary outcomes:
measure: Change from Baseline in Forced Expiratory Volume in the First Second (FEV1) Percent (%) Predicted over time during Asthma Exacerbation
timeFrame: Baseline and up to 5 days from the time asthma exacerbation is diagnosed
measure: Change from Baseline in Nasal Concentrations of Other Relevant Inflammatory Cytokines/Chemokines over time during Asthma Exacerbation
timeFrame: Baseline and up to 5 days from the time asthma exacerbation is diagnosed
measure: Correlation over time Between Changes in Nasal IL-1β Concentration from Baseline and Changes in FEV1 % Predicted from Baseline during Asthma Exacerbation
timeFrame: Baseline and up to 5 days from the time asthma exacerbation is diagnosed
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Allison Burbank, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007 Nov;120(5 Suppl):S94-138. doi: 10.1016/j.jaci.2007.09.043.