Clinical trial NCT02577497: Effect of Extra- Fine Versus Coarse-Particle Inhaled Corticosteroids (ICS) on Ventilation Heterogeneity in Children With Poorly Controlled Asthma
Official title: Effect of Extra- Fine Versus Coarse-Particle Inhaled Corticosteroids (ICS) on Ventilation Heterogeneity in Children With Poorly Controlled Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2015-10-16
Enrollment: 31
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to show that ventilation heterogeneity identified by hyperpolarized helium-3 lung MRI is prevalent children with poorly controlled asthma despite guidelines-based treatment with ICS. The secondary objective is to demonstrate whether or not eight weeks of treatment with extra-fine particle ICS (HFA-BDP) improves ventilation heterogeneity compared to treatment with a coarse particle ICS (fluticasone HFA or dry powder).


Eligibility criteria: Inclusion Criteria:

* Boys and girls between the ages of 6 and 17 years
* Diagnosis of asthma based on NAEPP3 criteria
* Poor asthma control based on one or more of the following criteria:

an ACT ≤ 19 and/or ACQ ≥ 1.5 units at the screening and/or randomization visits despite continuous or intermittent treatment with ICS and/or an anti-leukotriene within six months before enrollment.

* Any airflow obstruction based on Hankinson et al reference standards: FEV1 % \< 80% predicted, an FEV1/FVC ratio \< 90% predicted, and/or an FEF 25-75 \< 70% predicted at the screening and/or randomization visits.
* Frequent severe exacerbations as reflected by ≥ 2 bursts of systemic corticosteroids (≥ 3 days each) in the previous 12 months.
* Serious exacerbations reflected by at least one hospitalization, ICU stay, or mechanical ventilation in the previous 12 months
* "Not well controlled" by NAEPP or GINA asthma treatment guidelines
* For post-pubertal females, negative urine pregnancy screen and willing if sexually active (as counseled by a female study coordinator in private) to using a consistent and appropriate method of birth control for the duration of the study.

Exclusion Criteria:

* Premature birth \< 35 weeks estimated gestational age
* Maintenance oral prednisone (defined as daily or alternate day for the past three months before screening) or omalizumab treatment for asthma control
* Any significant medical condition that might inform maldistribution of ventilation apart from asthma including bronchiectasis, cardiac disease, congenital anomalies of the respiratory system, neurodevelopmental delay with cognitive impairment, ciliary dyskinesia syndromes, immune deficiency, recent lower respiratory infection (within six weeks of screen visit). Co-morbidities associated with asthma including sleep apnea syndrome, obesity, GERD, and right middle lobe syndrome are not criteria for exclusion.
* Claustrophobia, inner ear implants, aneurysm or other surgical clips, metal foreign bodies in the eye, pacemaker, or other contraindication to MR scanning. Subjects with any implanted device that cannot be verified as MRI compliant will be excluded.
* Chest circumference greater than that of the helium coil. The circumference of the coil is approximately 42 inches.
* Inability to understand simple instructions or to hold still for 10 seconds.

Primary outcomes:
measure: Ventilation Heterogeneity Index (VHI)
timeFrame: Baseline
Secondary outcomes:
measure: Change in Ventilation Heterogenity Index (VHI)
timeFrame: Baseline (week 0), week 12, week 16, and week 24
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia - Fontaine Research Park
state: Virginia
Study officials:
affiliation: University of Virginia
name: W. Gerald Teague, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gerald Teague W, Mata J, Qing K, Tustison NJ, Mugler JP, Meyer CH, de Lange EE, Shim YM, Wavell K, Altes TA. Measures of ventilation heterogeneity mapped with hyperpolarized helium-3 MRI demonstrate a T2-high phenotype in asthma. Pediatr Pulmonol. 2021 Jun;56(6):1440-1448. doi: 10.1002/ppul.25303. Epub 2021 Feb 23.