Therapeutic Relevance of Abnormal Airway Morphology in Asthma

NCT06970080 | Recruiting Phase 4

• 1 other identifier: Xe012
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 2

Brief Summary

Most individuals with asthma can effectively manage their symptoms and maintain normal lung function using inhaled medications, unfortunately, there is a subset of asthma sufferers whose symptoms, lung function, and risk of asthma attacks remain unimproved despite conventional inhaled medications. There could be several reasons for this. One possibility is that inhaled medications fail to reach the intended areas within the lungs, due to structural abnormalities within the airways themselves. Much like road conditions or closures can impede the speed and efficiency of vehicle travel, factors such as airway narrowing or mucus blockages, which are common in asthma, can obstruct the passage of inhaled medications through the airways. Our team has now optimized advanced medical imaging techniques, including magnetic resonance imaging (MRI) and computed tomography (CT), required to investigate this. This study will use these imaging methods to visually assess and measure individual patients' airways and determine whether abnormal airway structures impact how well they respond to inhaled and orally delivered medications. We anticipate finding that abnormal airway structures make inhaled medications less effective, but that they do not affect the response to oral medications.

Conditions

Asthma

Keywords

asthma; computed tomography; corticosteroids; inhaled drug deposition; magnetic resonance imaging; airway morphology; eosinophilic inflammation

Outcome Measures

Primary Outcomes (2)

• Biological response to additional ICS

  Biological response to additional ICS evaluated as change from baseline in sputum eosinophil percent and FeNO at 12 weeks.

  12 weeks

• Biological response to add-on OCS

  Biological response to add-on OCS evaluated as change from Phase II baseline (Visit 3/Week 12) in sputum eosinophil percent and FeNO at one-week (Visit 4/Week 13).

  1 week

Secondary Outcomes (20)

• 129Xe MRI ventilation defect percent (VDP) response to additional ICS

  12 weeks

• FEV1 response to additional ICS

  12 weeks

• Respiratory system resistance (Rrs) at 5Hz response to additional ICS

  12 weeks

• Respiratory system reactance (Xrs) at 5Hz response to additional ICS

  12 weeks

• Respiratory system resistance (Rrs) at 19Hz response to additional ICS

  12 weeks

Study Arms (1)

Uncontrolled eosinophilic asthma

EXPERIMENTAL

In Phase I, participants will receive a doubling of their current ICS dose. If their asthma remains uncontrolled, they will receive an OCS burst in phase II.

Drug: Inhaled corticosteroid (ICS); Drug: Oral Corticosteroid (OCS)

Interventions

Inhaled corticosteroid (ICS) DRUG

In Phase I, participants will receive additional same dose of extra-fine particle ICS (i.e., their ICS would be doubled) for 12-weeks.

Also known as: QVAR, hydrofloroalkaline-beclomethasone dipropionate

Uncontrolled eosinophilic asthma

Oral Corticosteroid (OCS) DRUG

In phase II, participants will receive add-on oral prednisone (30mg/day) for one-week.

Also known as: prednisone

Uncontrolled eosinophilic asthma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide written informed consent.
• Able and willing to comply with the study protocol.
• Males and females ≥ 18 years of age.
• Asthma diagnosed by a respiratory physician.
• Airway hyperresponsiveness (defined as methacholine PC20 ≤8mg/mL) and/or bronchodilator reversibility (defined as post-bronchodilator FEV1 improvement ≥200mL and 12%) in the last 6 months
• ACQ ≥1.5 during the screening period.
• Sputum eosinophils ≥3% and/or FeNO ≥35ppb during the screening period.

You may not qualify if:

• Current smoker, defined as someone having smoked ≥1 cigarette/day (or vape/pipe/cigar/marijuana) for ≥30 days within 12 months prior to screening.
• Pregnant or breastfeeding
• Non-English speaking
• Oral corticosteroids in past 1-month
• Biologic therapy in past 6-months
• Unable to perform proper MDI technique during the screening period
• Other pulmonary diseases (e.g., chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension, tuberculosis) requiring treatment within 12 months prior to screening.
• Unable to undergo MRI. Patient has an implanted mechanically, electrically, or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist). Suffers from any physical, psychological, or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia.

Sponsors & Collaborators

• McMaster University: lead

Study Sites (2)

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N4A6, Canada

RECRUITING

Western University

London, Ontario, N6A 3K7, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Asthma

Interventions

Beclomethasone; Adrenal Cortex Hormones; Prednisone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienediols

Central Study Contacts

Sarah Svenningsen, PhD

CONTACT

(905) 522-1155 Ext. 32195; svennins@mcmaster.ca

Yonni Friedlander, PhD

CONTACT

(905) 522-1155 Ext. 32195; yfriedla@stjoes.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 17, 2025
• First Posted: May 14, 2025
• Study Start: June 2, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: September 11, 2025

Record last verified: 2025-09

Locations

CA (2)