Ignite Creation Date:
2024-05-05 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00180661
Status:
COMPLETED
Last Update Posted:
2019-10-04
First Post:
2005-09-12
Brief Title:
Inflammation and Corticosteroid Responsiveness in Severe Asthma
Sponsor:
Imperial College London
Organization:
Imperial College London
Study Overview
Official Title:
Inflammation and Corticosteroid Responsiveness in Severe Asthma
Status:
COMPLETED
Status Verified Date:
2019-10
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:
SARP
Brief Summary:
Some patients with mild asthma may develop severe asthma It is not known what makes patients with mild asthma become severe and we plan to find out why this happens Patients with severe asthma may have a different type of inflammation in the airway tubes Patients with severe asthma do not get as much benefit from taking steroid inhalers or tablets compared to asthma patients with mild disease The study hypothesis is that the inflammation in severe asthma is such that it makes steroids less effective in treating asthma We will find out what possible abnormalities there are in the blood cells and the bronchoalveolar macrophage cells in the lungs of patients with severe asthma compared to those with mild or moderate asthma
Detailed Description:
Study Design Patients referred to the Royal Brompton Hospital with severe asthma will be entered into a protocol that will determine whether they have asthma and if so the severity and clinical features of their asthma Patients will also undergo investigations relating to asthma as detailed below We will use an agreed Severe Asthma Research protocol SARP screening system to diagnose asthma history bronchodilator response and presence of bronchial hyperresponsiveness Screening questionnaire in SARP Handbook Usually the protocol will be carried out while the patient is admitted over 3-night admission
Patients will undergo fiberoptic bronchoscopy We will obtain cells by bronchoalveolar lavage and bronchial biopsies of the airway mucosa These cells and biopsies will be studied in vitro as to the expression of corticosteroid receptor nuclear translocation expression of cytokines and the degree of histone acetylationdeacetylation status These findings will be compared to those cells and biopsies obtained from mild and moderately severe asthma
In a subgroup of patients with severe asthma patients will be treated with oral prednisolone 40 mgday or increase in maintenance dose of prednisolone by 40 mgday Fiberoptic bronchoscopy will then be repeated
Details of the interventions proposed Some of the interventions listed below are in routine clinical use for investigation of severe asthma For example the computed tomogram is only ordered on clinical grounds A fiberoptic bronchoscopy will be performed
1 Demographic history and history of their symptoms of asthma and treatments using a comprehensive questionnaire
2 Quality of life questionnaire AQLQ
3 Skin prick tests to 16 common allergens
4 Measuring lung function tests
5 Bronchial responsiveness to methacholine
6 Bronchial reversibility test to inhaled salbutamol
7 Keeping a diary card of symptoms treatments and peak flows for 2 weeks
8 Observance of compliance to treatments
9 Provision of sample of sputum spontaneous or induced
10 Measuring exhaled nitric oxide collecting of exhaled breath condensates
11 Fiberoptic bronchoscopy to obtain bronchoalveolar lavage cells bronchial brushings and bronchial biopsies
12 Obtaining sample of blood for DNA extraction for genetic analysis
13 Obtaining blood for blood mononuclear cells for in vitro analysis of the effects of corticosteroids In patients with mild-to-moderate asthma test 8 will not be performed The details of these interventions are enclosed in the SARP Handbook
Sources and Recruitment of Subjects
Patients will be recruited from all patients referred to the Royal Brompton Hospital with a referral diagnosis of severe or difficult asthma for further management The Royal Brompton Hospital is recognized nationally as a center for referral of such patients
7Inclusion criteria The final diagnosis of severe asthma will be made according to the screening steps we have set up The definition will require the presence of one or both major criteria treatment with continuous or near continuous oral corticosteroids andor requirement for treatment with high dose inhaled steroids and two minor criteria
Patients who do not fit the criteria of severe asthma will not be entered into the study
Age 18-60 both sexes
For the investigation of fiberoptic bronchoscopy other additional inclusion criteria will be imposed
1 Post-bronchodilator FEV1 greater than 40 on the day of the bronchoscopy
2 No evidence of an exacerbation of asthma within the past 4 weeks
3 Ability to cooperate with procedures
4 Ability to give consent
5 The bronchoscopist has determined the subject is clinically appropriate for bronchoscopy
Patients will be excluded for fiberoptic bronchoscopy if
1 FEV1 is less than 35 predicted before or less than 40 predicted after bronchodilator administration
2 Asthma is clinically unstable
3 Communication channels is not established for follow-up contacts
4 Clinically significant unstable co-morbidities are present
Exclusion criteria Current smokers and ex-smokers with greater than 10 pack years history of smoking
Pregnancy or unreliable contraceptive measures in child-bearing woman
Volunteer subjects We will need comparative asthmatic subjects with mild to moderately severe asthma The groups will be defined as follows according to their need for treatments as established in the Asthma Management GINA or BTS guidelines i Mild intermittent symptoms and need for reliever bronchodilator less than once a day ii moderate asthma well-controlled asthma with minimal symptoms while on inhaled corticosteroid therapy not exceeding 2000 microgram beclomethasone equivalent
These patients will be recruited from the Asthma clinics attending the Royal Brompton Hospital and also the milder patients will be recruited by advertisement within the Hospital or from local general practices
Current involvement in research The patients entered into this study will not be involved in any other research project and must have Completed any other project within a month of entry into the current study From previous experience we aim to recruit 12 patients with severe asthma per year in total 50 patients with severe asthma over a 4 year period Concomitantly we will recruit 40 mild-to-moderately severe asthma patients Pharmacology and Dispensing i substance Prednisolone tablets ii route of administration Oral iii frequency once a day iv dosage 30 mgday or addition of 30 mg on top of maintainence dose v stage of CSM evaluation na
Patients will undergo fiberoptic bronchoscopy We will obtain cells by bronchoalveolar lavage and bronchial biopsies of the airway mucosa These cells and biopsies will be studied in vitro as to the expression of corticosteroid receptor nuclear translocation expression of cytokines and the degree of histone acetylationdeacetylation status These findings will be compared to those cells and biopsies obtained from mild and moderately severe asthma
In a subgroup of patients with severe asthma patients will be treated with oral prednisolone 40 mgday or increase in maintenance dose of prednisolone by 40 mgday Fiberoptic bronchoscopy will then be repeated
Details of the interventions proposed Some of the interventions listed below are in routine clinical use for investigation of severe asthma For example the computed tomogram is only ordered on clinical grounds A fiberoptic bronchoscopy will be performed
1 Demographic history and history of their symptoms of asthma and treatments using a comprehensive questionnaire
2 Quality of life questionnaire AQLQ
3 Skin prick tests to 16 common allergens
4 Measuring lung function tests
5 Bronchial responsiveness to methacholine
6 Bronchial reversibility test to inhaled salbutamol
7 Keeping a diary card of symptoms treatments and peak flows for 2 weeks
8 Observance of compliance to treatments
9 Provision of sample of sputum spontaneous or induced
10 Measuring exhaled nitric oxide collecting of exhaled breath condensates
11 Fiberoptic bronchoscopy to obtain bronchoalveolar lavage cells bronchial brushings and bronchial biopsies
12 Obtaining sample of blood for DNA extraction for genetic analysis
13 Obtaining blood for blood mononuclear cells for in vitro analysis of the effects of corticosteroids In patients with mild-to-moderate asthma test 8 will not be performed The details of these interventions are enclosed in the SARP Handbook
Sources and Recruitment of Subjects
Patients will be recruited from all patients referred to the Royal Brompton Hospital with a referral diagnosis of severe or difficult asthma for further management The Royal Brompton Hospital is recognized nationally as a center for referral of such patients
7Inclusion criteria The final diagnosis of severe asthma will be made according to the screening steps we have set up The definition will require the presence of one or both major criteria treatment with continuous or near continuous oral corticosteroids andor requirement for treatment with high dose inhaled steroids and two minor criteria
Patients who do not fit the criteria of severe asthma will not be entered into the study
Age 18-60 both sexes
For the investigation of fiberoptic bronchoscopy other additional inclusion criteria will be imposed
1 Post-bronchodilator FEV1 greater than 40 on the day of the bronchoscopy
2 No evidence of an exacerbation of asthma within the past 4 weeks
3 Ability to cooperate with procedures
4 Ability to give consent
5 The bronchoscopist has determined the subject is clinically appropriate for bronchoscopy
Patients will be excluded for fiberoptic bronchoscopy if
1 FEV1 is less than 35 predicted before or less than 40 predicted after bronchodilator administration
2 Asthma is clinically unstable
3 Communication channels is not established for follow-up contacts
4 Clinically significant unstable co-morbidities are present
Exclusion criteria Current smokers and ex-smokers with greater than 10 pack years history of smoking
Pregnancy or unreliable contraceptive measures in child-bearing woman
Volunteer subjects We will need comparative asthmatic subjects with mild to moderately severe asthma The groups will be defined as follows according to their need for treatments as established in the Asthma Management GINA or BTS guidelines i Mild intermittent symptoms and need for reliever bronchodilator less than once a day ii moderate asthma well-controlled asthma with minimal symptoms while on inhaled corticosteroid therapy not exceeding 2000 microgram beclomethasone equivalent
These patients will be recruited from the Asthma clinics attending the Royal Brompton Hospital and also the milder patients will be recruited by advertisement within the Hospital or from local general practices
Current involvement in research The patients entered into this study will not be involved in any other research project and must have Completed any other project within a month of entry into the current study From previous experience we aim to recruit 12 patients with severe asthma per year in total 50 patients with severe asthma over a 4 year period Concomitantly we will recruit 40 mild-to-moderately severe asthma patients Pharmacology and Dispensing i substance Prednisolone tablets ii route of administration Oral iii frequency once a day iv dosage 30 mgday or addition of 30 mg on top of maintainence dose v stage of CSM evaluation na
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