Ignite Creation Date:
2025-12-25 @ 4:56 AM
Ignite Modification Date:
2025-12-26 @ 3:56 AM
Study NCT ID:
NCT05280418
Status:
RECRUITING
Last Update Posted:
2024-01-05
First Post:
2022-02-11
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Tezepelumab on Airway Structure and Function in Patients With Uncontrolled Moderate-to-severe Asthma
Sponsor:
McMaster University
Organization:
Study Overview
Official Title:
A Two-arm, Placebo-controlled, Randomized Clinical Trial to Evaluate the Effect of Tezepelumab on Airway Structure and Function in Patients With Uncontrolled Moderate-to-severe Asthma
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In adult patients with uncontrolled moderate-to-severe asthma, blocking TSLP with tezepelumab will improve ventilation heterogeneity (evaluated by hyperpolarized 129Xe MRI), and this will be associated with reduced airway inflammation (evaluated by sputum composition), luminal narrowing and plugging (evaluated by CT).
Detailed Description:
The luminal obstruction in asthma that contributes to symptoms is due to inflammatory cells (usually eosinophils or neutrophils), mucus, smooth muscle constriction, airway wall thickness, or a combination of the above. This obstruction can be regionally visualized and quantified by computed tomography (CT), and its functional consequence can be assessed at high resolution using inhaled hyperpolarized 129Xe gas magnetic resonance imaging (MRI). Thymic stromal lymphopoietin (TSLP), an epithelial cell derived cytokine that is produced in response to environmental and proinflammatory stimuli, may contribute to all of these features of asthma through its downstream effects on a wide variety of immune (e.g. eosinophils, mast cells, group 2 innate lymphoid cells (ILC2s), Th2 cell, and Th17 cells) and structural cells (e.g. smooth muscle cells, and fibroblasts). Of note, TSLP is believed to upregulate multiple downstream inflammatory pathways, including IL-4, IL-5 and IL-13 signalling. It is also believed to mediate structural mechanisms that contribute to airway remodelling and smooth muscle dysfunction.
The consequence of blocking TSLP with tezepelumab on airway structure and function has not been investigated. This study will use CT to quantify airway wall and lumen structure according to previously described methods. CT images will also be evaluated for intraluminal plugging and a visual mucus score will be generated. Ventilation heterogeneity in asthmatics, the functional consequence of luminal obstruction, can be regionally measured with high temporal and spatial resolution using inhaled hyperpolarized gas MRI. In asthmatics, focal ventilation defects are observed and these have been shown to be spatially related to airway abnormalities and to respond to bronchoconstriction, bronchodilation, and anti-T2 biologics.
Due to the potential effect of tezepelumab on luminal inflammation, smooth muscle dysfunction and mucus hypersecretion, it is believed that MRI-detectable improvements in ventilation heterogeneity will be observed in asthmatics.
The consequence of blocking TSLP with tezepelumab on airway structure and function has not been investigated. This study will use CT to quantify airway wall and lumen structure according to previously described methods. CT images will also be evaluated for intraluminal plugging and a visual mucus score will be generated. Ventilation heterogeneity in asthmatics, the functional consequence of luminal obstruction, can be regionally measured with high temporal and spatial resolution using inhaled hyperpolarized gas MRI. In asthmatics, focal ventilation defects are observed and these have been shown to be spatially related to airway abnormalities and to respond to bronchoconstriction, bronchodilation, and anti-T2 biologics.
Due to the potential effect of tezepelumab on luminal inflammation, smooth muscle dysfunction and mucus hypersecretion, it is believed that MRI-detectable improvements in ventilation heterogeneity will be observed in asthmatics.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: