Effect of Extra- Fine Versus Coarse-Particle Inhaled Corticosteroids (ICS) on Ventilation Heterogeneity in Children With Poorly Controlled Asthma

NCT ID: NCT02577497

Last Updated: 2018-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2018-07-06

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).

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Beclomethasone

Subjects are being randomized to 8 weeks of beclomethasone or fluticasone treatment followed by a 4 week study drug washout with resumption of standard asthma medication regimen for 4 weeks, followed by 8 weeks of beclomethasone or fluticasone (whichever drug was not taken the first 8 weeks)

Group Type: EXPERIMENTAL

beclomethasone

Intervention Type: DRUG

fluticasone

Subjects are being randomized to 8 weeks of beclomethasone or fluticasone treatment followed by a 4 week study drug washout with resumption of standard asthma medication regimen for 4 weeks, followed by 8 weeks of beclomethasone or fluticasone (whichever drug was not taken the first 8 weeks)

Group Type: EXPERIMENTAL

fluticasone

Intervention Type: DRUG

Interventions

beclomethasone

Intervention Type: DRUG

fluticasone

Intervention Type: DRUG

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Willliam Gerald Teague

Chief, Division of Respiratory Medicine, Allergy, and Immunology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

W. Gerald Teague, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia - Fontaine Research Park

Charlottesville, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33621442 (View on PubMed)

Other Identifiers

18422

Identifier Type: -

Identifier Source: org_study_id