Ignite Creation Date:
2024-05-06 @ 8:02 PM
Last Modification Date:
2024-10-26 @ 3:19 PM
Study NCT ID:
NCT06224634
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-10
First Post:
2024-01-16
Brief Title:
The Effect of Anti-IL17 on Airway Hyperresponsiveness and Resistance
Sponsor:
Copenhagen University Hospital Hvidovre
Organization:
Copenhagen University Hospital Hvidovre
Study Overview
Official Title:
The Effect of Anti-IL17 on Airway Hyperresponsiveness and Resistance A Longitudinal Cohort Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
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:
This observational longitudinal cohort study aims to assess the effect of monoclonal antibodies targeting interleukin 17 anti-IL-17 on airway hyperreactivity and airway resistance The study involves adult participants suffering from dermatological or rheumatological illness who are planning to start treatment with monoclonal antibodies targeting interleukin 17 as a part of the treatment of these diseases
The primary outcome of this study will be changes in airway hyperresponsiveness to methacholine challenge reported as response-dose-ratio before and after initiation of anti-IL17 treatment regardless of presence of respiratory disease Furthermore the potential effect of anti-IL-17 on airway resistance will be assessed using conventional spirometry for measuring changes in FEV1 and Airwave oscillometry
A reduced degree of airway hyperreactivity and airway resistance after initiating ani-IL-17 could indicate effectiveness of anti-IL-17 in asthma patients which would have to be examined further in a population of asthma patients
The primary outcome of this study will be changes in airway hyperresponsiveness to methacholine challenge reported as response-dose-ratio before and after initiation of anti-IL17 treatment regardless of presence of respiratory disease Furthermore the potential effect of anti-IL-17 on airway resistance will be assessed using conventional spirometry for measuring changes in FEV1 and Airwave oscillometry
A reduced degree of airway hyperreactivity and airway resistance after initiating ani-IL-17 could indicate effectiveness of anti-IL-17 in asthma patients which would have to be examined further in a population of asthma patients
Detailed Description:
Background
Antibodies towards interleukin 17 IL-17 are approved for treating various rheumatological and dermatological diseases like psoriatic arthritis ankylosing spondylitis and plaque psoriasis In recent years IL-17 has been suggested as a potential driver of severe non-Type 2 asthma because of its association with glucocorticoid resistance and symptoms of severe asthma Since conventional treatment is often less effective in patients suffering from non-Type 2 asthma sometimes adequate disease control cannot be achieved thus limiting these patients opportunity for physical exercise and thereby increasing the risk of obesity and heart disease Furthermore obesity has been shown to increase asthma symptoms and frequency of exacerbations
IL-17 has shown to be upregulated by female sex hormones which may explain the sex specific traits of severe non-Type 2 asthma In obese mice IL-17 has shown to be directly responsible for the induction of airway hyperresponsiveness AHR thus making it a potential target for treatment It is especially of interest that none of the previously performed human studies have investigated the effect of blocking IL-17 on AHR A previous study investigating the effect of blocking IL-17 on lung function measured as change in FEV1 forced expiratory volume in 1 second in moderate to severe patients with asthma did not find any significant effect However this study included both men and women as well as lean and obese participants which could explain the lack of clinical difference Another previous study also showed no effect of anti-IL17 in general However this study showed that those with the greatest reversibility to bronchodilators had the best improvement in symptoms Although negative these studies brought us further by showing that anti-IL-17 treatment was safe and tolerable for patients with moderate to severe asthma Oscillometry has been known for several decades but is only on its way into clinical practice Oscillometry is more sensitive than spirometry in detecting small airway disease and AHR Thus using oscillometry in studies investigating airway resistance in asthmatic individuals in addition to spirometry is warranted
Objectives The overall objective of this study is to determine whether AHR and airway resistance is reduced when initiating treatment with anti-IL17 antibodies for other indications than pulmonary disease Changes in AHR to methacholine challenge will be reported as response-dose-ratio before and after initiation of anti-IL17 Airway resistance will be assessed using both conventional spirometry for measuring changes in FEV1 and Airwave oscillometry
Hypothesis
Primary hypothesis In rheumatologic and dermatological patients commencing anti-IL-17 for other reasons than pulmonary disease we expect a reduction in airway responsiveness to methacholine challenge after 2-4 months of treatment when compared to prior to initiation of anti-IL-17 treatment
Secondary hypotheses Anti-IL17 treatment will show no effect on FEV1 measured using conventional spirometry but will improve measures of airwave oscillometry
Antibodies towards interleukin 17 IL-17 are approved for treating various rheumatological and dermatological diseases like psoriatic arthritis ankylosing spondylitis and plaque psoriasis In recent years IL-17 has been suggested as a potential driver of severe non-Type 2 asthma because of its association with glucocorticoid resistance and symptoms of severe asthma Since conventional treatment is often less effective in patients suffering from non-Type 2 asthma sometimes adequate disease control cannot be achieved thus limiting these patients opportunity for physical exercise and thereby increasing the risk of obesity and heart disease Furthermore obesity has been shown to increase asthma symptoms and frequency of exacerbations
IL-17 has shown to be upregulated by female sex hormones which may explain the sex specific traits of severe non-Type 2 asthma In obese mice IL-17 has shown to be directly responsible for the induction of airway hyperresponsiveness AHR thus making it a potential target for treatment It is especially of interest that none of the previously performed human studies have investigated the effect of blocking IL-17 on AHR A previous study investigating the effect of blocking IL-17 on lung function measured as change in FEV1 forced expiratory volume in 1 second in moderate to severe patients with asthma did not find any significant effect However this study included both men and women as well as lean and obese participants which could explain the lack of clinical difference Another previous study also showed no effect of anti-IL17 in general However this study showed that those with the greatest reversibility to bronchodilators had the best improvement in symptoms Although negative these studies brought us further by showing that anti-IL-17 treatment was safe and tolerable for patients with moderate to severe asthma Oscillometry has been known for several decades but is only on its way into clinical practice Oscillometry is more sensitive than spirometry in detecting small airway disease and AHR Thus using oscillometry in studies investigating airway resistance in asthmatic individuals in addition to spirometry is warranted
Objectives The overall objective of this study is to determine whether AHR and airway resistance is reduced when initiating treatment with anti-IL17 antibodies for other indications than pulmonary disease Changes in AHR to methacholine challenge will be reported as response-dose-ratio before and after initiation of anti-IL17 Airway resistance will be assessed using both conventional spirometry for measuring changes in FEV1 and Airwave oscillometry
Hypothesis
Primary hypothesis In rheumatologic and dermatological patients commencing anti-IL-17 for other reasons than pulmonary disease we expect a reduction in airway responsiveness to methacholine challenge after 2-4 months of treatment when compared to prior to initiation of anti-IL-17 treatment
Secondary hypotheses Anti-IL17 treatment will show no effect on FEV1 measured using conventional spirometry but will improve measures of airwave oscillometry
Study Oversight
Has Oversight DMC:
None
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?:
None