REverse LuNg Airway and Vascular RemOdeling in Asthma ReMission (ReNORM)

NCT07174713 | Not Yet Recruiting

• 1 other identifier: ROB0061
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

In this program of research, the investigators aim to answer the question: In patients with asthma aged 18-80, how do the lung airways and vessels respond to biologic therapy and what role does age and asthma duration have in this response? While about 4.6 million Canadians live with asthma, \~5-10% of patients have severe asthma meaning that multiple inhaled and systemic oral corticosteroid treatments have failed to improve symptoms and exacerbations, leading to lost work and school days and substantially diminished ability to participate in normal life. For such people, the vast majority of whom are middle aged and remember asthma as part of their entire lifespan, biologic immunomodulator therapies, which block the function of asthma inflammatory pathways, provide a final step-up therapy option. There is emerging evidence that prescribed in the right patient at the right time, the right biologic can result in clinical remission of asthma. While spontaneous clinical remission of asthma is rare, it has been documented in children in whom lung growth and remodeling is still possible. It remains unknown whether clinical remission in adults is accompanied by the reversal of pathologic remodeling, at the level of the airways and pulmonary vessels. This is critical to elucidate as investigators and physicians move forward with currently proposed criteria for "complete asthma remission". The inconvenient truth about asthma and age is that in older adult lungs, exposed to years of infection, exacerbations, smooth muscle remodeling and pulmonary vascular shunt, the mechanisms by which complete pathologic remission may be achieved are complex and poorly understood. To address this knowledge gap, the investigators will evaluate 150 patients (Vancouver, Ottawa, Hamilton, London) (in three age tertiles 18-29; 30-59; 60-80) with severe asthma and 50 age- and sex matched healthy volunteers over 2-years using chest CT, MRI and pulmonary function tests. The investigators will use the pulmonary imaging measurements to generate an imaging-index of normal airway structure and function which will be compared with and significantly correlate with MR-guided bronchoscopic sample measurements made before and after 1-/2-years of treatment. The investigators will reveal the pathobiologic relationship between age, asthma duration, clinical remission and imaging normalization with direct comparison to histology-based airway measurements.

Conditions

Asthma; Eosinophilic

Keywords

Hyperpolarized Xenon MRI; Clinical Remission; Biologic Therapy; Airway Remodeling

Outcome Measures

Primary Outcomes (7)

• Determine extent of imaging-based remission in patients with severe asthma following 1 and 2 years of biologic therapy

  Measured using 129Xe ventilation defect percent (VDP)

  from baseline to year 1 and year 2

• Measure the extent and timing of clinical remission in patients with severe asthma as measured by changes in spirometry measurements of FEV1 and FVC

  Measured using forced expiratory volume in 1 second and forced vital capacity

  from baseline to 1 year and 2 years

• To determine the extent and timing of clinical remission in patients with severe asthma using symptoms scores of ACQ-5 and ACT

  Measured using changes in asthma control questionnaire and asthma control test

  From baseline to 1 year and 2 years

• Determine the extent and timing of imaging-based remission in patients with severe asthma using CT airway and vessel morphology

  Measured using computed tomography (CT) airway and vessel metrics

  From baseline to 1 year and 2 years

• To determine the extent and timing of clinical remission using the clinical outcome of frequency of asthma exacerbations in patients with severe asthma

  Measured using the number of asthma exacerbations

  from baseline to 1 year and 2 years

• To determine the extent and timing of clinical remission of patients with severe asthma using the clinical outcome of OCS use

  Measured by the frequency of oral corticosteroid usage

  From baseline to 1 year and 2 years

• Determine the extent and timing of clinical remission in patients with severe asthma as measured by sputum and blood eosinophil counts

  Measured using blood and sputum eosinophil counts

  From baseline to 1 year and 2 years

Secondary Outcomes (17)

• Timing and proportion of patients achieving clinical remission after biologic treatment as measured by FEV1 and FVC.

  From baseline to 1 year and 2 years

• To determine the timing and proportion of patients achieving clinical remission as measured by ACQ-5 and ACT questionnaires.

  From baseline to 1 year and 2 years

• Determine the timing and proportion of patients with severe asthma achieving clinical remission after biologic treatment using FeNO.

  From baseline to 1 year and 2 years

• Determine the timing and proportion of patients with severe asthma achieving clinical remission using DLco.

  From baseline to 1 year and 2 years

• Determine the timing and proportion of patients with severe asthma achieving clinical remission after biologic treatment using SGRQ score.

  From baseline to 1 year and 2 years.

Other Outcomes (3)

• Quantify the relationships of imaging and pathologic markers of remodeling and develop a non-invasive imaging-index lung normalization.

  From baseline (Day 0) to year 2

• Quantify the relationships of imaging and pathologic markers of remodeling and develop a non-invasive imaging-index lung normalization using MRI/CT correlations with histologic changes

  From baseline to 2 years.

• Quantify the relationships of imaging and pathologic markers of remodeling and develop a non-invasive imaging-index lung normalization using MRI/CT fusion data

  From baseline to 2 years.

Study Arms (2)

Asthma - Biologic Therapy

EXPERIMENTAL

Participants with severe asthma (GINA 5) who are eligible to begin biologic therapy. Participants will undergo serial assessment with pulmonary imaging (CT, MRI), lung function testing, sputum collection, and symptom questionnaires. A subset of participants (\~15%) will be randomized to undergo MRI-guided bronchoscopy with airway sampling at baseline and 2 years.

Biological: Biologic Therapy

Healthy Control

NO INTERVENTION

Age- and sex-matched healthy participants with no history of lung disease. Participants will undergo pulmonary imaging (CT, MRI) and lung function testing at baseline and follow-up for comparison with the asthma group. No therapeutic intervention will be provided.

Interventions

Biologic Therapy BIOLOGICAL

Participants with severe asthma (GINA 5) who are eligible to begin biologic therapy. Participants will undergo serial assessment with pulmonary imaging (CT, MRI), lung function testing, sputum collection, and symptom questionnaires. A subset of participants (\~15%) will be randomized to undergo MRI-guided bronchoscopy with airway sampling at baseline and 2 years.

Asthma - Biologic Therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant understands study procedures and is willing to participate in the study as indicated by the patient's signature.
• Provision of written, informed consent prior to any study specific procedures.
• Males and females aged 18 to 80 years.
• Either diagnosed with severe asthma (GINA Step 5) and newly eligible for biologic therapy (based on ACQ-5, current treatment, exacerbation history, and blood eosinophils in accordance with approved criteria for omalizumab, mepolizumab, benralizumab, dupilumab, or tezepelumab), or a healthy volunteer with no history of chronic lung disease, matched by age and sex. Healthy participants must have a lifetime combustible tobacco and/or cannabis (including vaping) consumption of ≤5 pack-years.
• Women of childbearing potential (after menarche) must ensure that they are using an effective form of birth control for at least 2 months prior to each imaging visit. Examples of effective birth control include:
• True sexual abstinence
• A vasectomized sexual partner
• Implanon®
• Female sterilization by tubal occlusion
• Effective intrauterine device (IUD)/levonogestrel intrauterine system (IUS)
• Depo-Provera™ injections
• Oral contraceptive
• Evra Patch™
• Nuvaring™
• Women of childbearing potential (after menarche) must agree to use a highly effective form of birth control, as defined above, from enrollment, throughout the study duration, and 8 weeks after last dose of study drug, with negative urine pregnancy test result at Visit 1-5.

You may not qualify if:

• 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).
• In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI or CT, such as severe claustrophobia.
• Participants who are pregnant, breastfeeding or have a positive pregnancy test at initial screening visit.
• Participant is unable to perform spirometry or plethysmography maneuvers.
• Participant is unable to perform MRI and CT breath-hold maneuvers.

Sponsors & Collaborators

• Western University, Canada: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Robarts Research Institute; The University of Western Ontario

London, Ontario, N6A 5B7, Canada

Location

MeSH Terms

Conditions

Pulmonary Eosinophilia; Airway Remodeling

Interventions

Biological Therapy

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Grace Parraga, PhD

  Robarts Research Institute, The University of Western Ontario

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Grace Parraga, PhD

CONTACT

519-931-5777; gparraga@robarts.ca

Angela Wilson, RRT

CONTACT

519-931-5777; awilson@robarts.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Parallel assignment of participants to one of two arms: (1) patients with severe asthma initiating biologic therapy, and (2) healthy volunteers serving as controls. Asthma patients are followed over 2 years to assess clinical, imaging, and histologic responses to biologic treatment. A randomized subset of asthma participants undergoes MRI-guided bronchoscopy to correlate imaging with histopathology.

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: September 16, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: September 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)