Ignite Creation Date:
2024-05-06 @ 6:41 PM
Last Modification Date:
2024-10-26 @ 2:53 PM
Study NCT ID:
NCT05752019
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-09-07
First Post:
2022-11-15
Brief Title:
TAAI Erasmus Research Initiative to Fight CF Monitoring Inflammation in CF Lung Disease Into a New Era
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
TAAI Erasmus Research Initiative to Fight CF Monitoring Inflammation in CF Lung Disease Into a New Era
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-09
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:
TERRIFIC-MILE
Brief Summary:
Progressive destruction of the lungs is the main cause of shortened life expectancy in people with cystic fibrosis pwCF Inflammation and respiratory infections play a key role in CF lung disease Previous studies have shown that an increase in inflammatory markers predicts structural lung damage Close monitoring of pwCF is crucial to adequately provide optimal care Pulmonary management for pwCF involves treating infections and exacerbations and promoting exercise and mucociliary clearance to slow or prevent structural lung damage To evaluate the treatment and incite timely interventions it is important for the pulmonary physician to be well-informed about the condition of the lungs
The main monitoring tools in regular CF care are lung function sputum cultures symptom reporting and more recently imaging by chest computed tomography CT-scan or magnetic resonance imaging MRI Strangely enough there are currently no monitoring tools used in clinics to measure inflammation in the lung although this is a main factor for progressive lung disease
New highly effective modulator therapy HEMT such as elexacaftortezacaftorivacaftor ETI Kaftrio is transforming CF treatment vastly improving lung function and reducing exacerbations Initial CFTR modulators like ivacaftor and lumacaftorivacaftor also improved lung function and reduced exacerbations but studies showed that lung inflammation was still present The long-term impact of ETI and its effect on inflammation is not yet known
Thus monitoring pwCF on HEMT may be different from before as lung damage seen on chest CT will be less apparent and lung function will improve considerably therefore not being adequate markers for subtle changes in the lungs Thus the focus of monitoring in the era of highly effective CFTR modulators needs to change preferably focusing on measuring lung inflammation
An ideal monitoring tool for lung inflammation in pwCF should be non-invasive efficient and provide accurate and sensitive results Currently sputum and BAL are the most common methods for assessing inflammation but BAL is invasive and sputum may not always be available Exhaled breath analysis by the electronic nose eNose or gas chromatography-mass spectrometry GC-MS of volatile organic compounds VOCs shows promise as a non-invasive monitoring tool Other promising markers and techniques are inflammatory markers in the blood cytokines and micro-RNA miRNA and urine
Thus the objective of this project is to design novel minimally invasive monitoring techniques capable of identifying lung inflammation in pwCF undergoing highly effective CFTR modulator therapy ETI compared to those not using CFTR modulators The efficacy of these innovative techniques will be evaluated and verified against inflammatory markers in sputum spirometry and validated symptom and quality of life scores
The main monitoring tools in regular CF care are lung function sputum cultures symptom reporting and more recently imaging by chest computed tomography CT-scan or magnetic resonance imaging MRI Strangely enough there are currently no monitoring tools used in clinics to measure inflammation in the lung although this is a main factor for progressive lung disease
New highly effective modulator therapy HEMT such as elexacaftortezacaftorivacaftor ETI Kaftrio is transforming CF treatment vastly improving lung function and reducing exacerbations Initial CFTR modulators like ivacaftor and lumacaftorivacaftor also improved lung function and reduced exacerbations but studies showed that lung inflammation was still present The long-term impact of ETI and its effect on inflammation is not yet known
Thus monitoring pwCF on HEMT may be different from before as lung damage seen on chest CT will be less apparent and lung function will improve considerably therefore not being adequate markers for subtle changes in the lungs Thus the focus of monitoring in the era of highly effective CFTR modulators needs to change preferably focusing on measuring lung inflammation
An ideal monitoring tool for lung inflammation in pwCF should be non-invasive efficient and provide accurate and sensitive results Currently sputum and BAL are the most common methods for assessing inflammation but BAL is invasive and sputum may not always be available Exhaled breath analysis by the electronic nose eNose or gas chromatography-mass spectrometry GC-MS of volatile organic compounds VOCs shows promise as a non-invasive monitoring tool Other promising markers and techniques are inflammatory markers in the blood cytokines and micro-RNA miRNA and urine
Thus the objective of this project is to design novel minimally invasive monitoring techniques capable of identifying lung inflammation in pwCF undergoing highly effective CFTR modulator therapy ETI compared to those not using CFTR modulators The efficacy of these innovative techniques will be evaluated and verified against inflammatory markers in sputum spirometry and validated symptom and quality of life scores
Detailed Description:
Objective
The overall aim of the study is to develop innovative minimally invasive monitoring techniques that can identify lung inflammation in pwCF when using highly effective modulators compared to patients whom are not eligible for CFTR modulators control group yet
Primary objective is to assess whether measuring VOCs with GC-MS is a sensitive method to monitor changes in lung inflammation in pwCF
Secondary objectives are
To assess whether eNose is a sensitive method to monitor changes in lung inflammation in pwCF
To explore the usefulness of other inflammatory markers in blood and urine
Study design Explorative cohort study aimed to develop innovative minimally invasive monitoring techniques that can identify lung inflammation in pwCF when using highly effective CFTR modulators eNose GC-MS inflammatory markers in urine and blood compared to a control group pwCF not using CFTR modulators Furthermore the investigators will compare these techniques with inflammatory markers in induced sputum conventional spirometry symptom and quality of life scores
Study population pwCF older than 6 years of age who are eligible to start on ETI treatment and as a control group pwCF who are not on CFTR modulators
Intervention Subjects will be included till at least 3 study visits have taken place during treatment with ETI or for the control group 3 consecutive regular outpatient clinic visits which are usually 3 months apart If the subject has not started with ETI an extra visit at baseline will be added just before start of ETI At the study visits routine care checks will be done such as spirometry and blood sampling for liver enzyme monitoring The extra investigations performed at these study visits are exhaled breath sampling 3 extra vials of blood urine collection induced sputum Lung clearance index LCI will be done for subjects below 18 years of age Subjects may opt out for blood induced sputum and urine samples there always need to be an exhaled breath sampling with eNose and GC-MS If the patient has a contra-indication or does not want to participate in the induced sputum procedure the investigators will attempt to collect spontaneous expectorated sputum instead
To limit their burden of the study for the age group 6-11 the investigators will not conduct all measurements in that age group Resulting in the following difference in study design between two age groups
Patients 12 years At all visits there will be exhaled breath sampling 3 extra vials of blood with a blooddraw induced sputum urine sample and 2 questionnaires QoL and symptom score
Patients 12 years At all visits there will be exhaled breath sampling and 1 questionnaire symptom score will be done by doing an interview with the child On the last visit 2 extra vials of blood will be collected For patients 6-18 years of age a multiple breath washout MBW for LCI will be scheduled at study visits
Main study parametersendpoints
Primary endpoint is the comparison of VOCs measured by GC-MS during ETI treatment compared to control group over time during 3 different study visits
Secondary endpoints entail the correlation of VOCs by GC-MS breath profilesVOCs measured by eNose inflammatory markers in induced sputum IL-8 free neutrophilic elastase NE calprotectin and myeloperoxidase plus a predetermined cytokine panel blood IL-18 IL-1β TNF hsCRP sCD14 calprotectin HGMB-1 amyloid and miRNA urine and lung function quality of life and symptom scores at baseline if available and overtime during 3 consecutive study visits In addition the change of VOCs by GC-MS and eNose from baseline till 3 months of ETI treatment will be investigated
The overall aim of the study is to develop innovative minimally invasive monitoring techniques that can identify lung inflammation in pwCF when using highly effective modulators compared to patients whom are not eligible for CFTR modulators control group yet
Primary objective is to assess whether measuring VOCs with GC-MS is a sensitive method to monitor changes in lung inflammation in pwCF
Secondary objectives are
To assess whether eNose is a sensitive method to monitor changes in lung inflammation in pwCF
To explore the usefulness of other inflammatory markers in blood and urine
Study design Explorative cohort study aimed to develop innovative minimally invasive monitoring techniques that can identify lung inflammation in pwCF when using highly effective CFTR modulators eNose GC-MS inflammatory markers in urine and blood compared to a control group pwCF not using CFTR modulators Furthermore the investigators will compare these techniques with inflammatory markers in induced sputum conventional spirometry symptom and quality of life scores
Study population pwCF older than 6 years of age who are eligible to start on ETI treatment and as a control group pwCF who are not on CFTR modulators
Intervention Subjects will be included till at least 3 study visits have taken place during treatment with ETI or for the control group 3 consecutive regular outpatient clinic visits which are usually 3 months apart If the subject has not started with ETI an extra visit at baseline will be added just before start of ETI At the study visits routine care checks will be done such as spirometry and blood sampling for liver enzyme monitoring The extra investigations performed at these study visits are exhaled breath sampling 3 extra vials of blood urine collection induced sputum Lung clearance index LCI will be done for subjects below 18 years of age Subjects may opt out for blood induced sputum and urine samples there always need to be an exhaled breath sampling with eNose and GC-MS If the patient has a contra-indication or does not want to participate in the induced sputum procedure the investigators will attempt to collect spontaneous expectorated sputum instead
To limit their burden of the study for the age group 6-11 the investigators will not conduct all measurements in that age group Resulting in the following difference in study design between two age groups
Patients 12 years At all visits there will be exhaled breath sampling 3 extra vials of blood with a blooddraw induced sputum urine sample and 2 questionnaires QoL and symptom score
Patients 12 years At all visits there will be exhaled breath sampling and 1 questionnaire symptom score will be done by doing an interview with the child On the last visit 2 extra vials of blood will be collected For patients 6-18 years of age a multiple breath washout MBW for LCI will be scheduled at study visits
Main study parametersendpoints
Primary endpoint is the comparison of VOCs measured by GC-MS during ETI treatment compared to control group over time during 3 different study visits
Secondary endpoints entail the correlation of VOCs by GC-MS breath profilesVOCs measured by eNose inflammatory markers in induced sputum IL-8 free neutrophilic elastase NE calprotectin and myeloperoxidase plus a predetermined cytokine panel blood IL-18 IL-1β TNF hsCRP sCD14 calprotectin HGMB-1 amyloid and miRNA urine and lung function quality of life and symptom scores at baseline if available and overtime during 3 consecutive study visits In addition the change of VOCs by GC-MS and eNose from baseline till 3 months of ETI treatment will be investigated
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MEC-2021-0907 | OTHER | Medical ethics committee | None |