Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001109695
Ethics application status
Approved
Date submitted
1/10/2014
Date registered
20/10/2014
Date last updated
20/10/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to investigate the underlying molecular characteristics of allergic asthma
Scientific title
A study to investigate the underlying molecular characteristics of allergic asthma by comparing biomarkers in the airways or blood among healthy subjects, mild and severe asthmatics.
Secondary ID [1] 285427 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild to moderate asthma 293186 0
Severe allergic asthma 293224 0
Condition category
Condition code
Respiratory 293460 293460 0 0
Asthma
Inflammatory and Immune System 293493 293493 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: Subjects with mild to moderate allergic asthma (n=20)who are controlled on inhaled corticosteroids will be asked to withdraw their inhaled corticosteroids (ICS) immediately following a 2 week run-in prior to an 8 week observational period. Subjects will visit the clinic every two weeks where their asthma status will be assessed.

Group 2: Subjects who have attended the severe asthma clinic at the John Hunter Hospital and are deemed suitable under current PBS guidelines for add on therapy for difficult asthma with omalizumab (Xolair) will be recruited to an observational study during their 6 month Xolair trial. Xolair administration will follow standard therapeutic guidelines and be administered every 2 or 4 weeksby the Xolair clinic nurse. The dose of omalizumab for each patient is detrmined by IgE levels and body weight. Frequency of dosing is determined by clinical status as assessed by the supervising physician. For the purposes of this study this group of subjects will be seen once per month only. If omalizumab is administered fortnightly, subjects enrolled in this study will be seen every second omalizumab injection.

Group 3: Healthy control volunteers will be recruited (n=20) to provide induced sputum and bloods samples for comparison to groups 1 & 2. The length of study involvement for this group will be dependent on the availablility of the subject to attend a post-baseline clinic visit if the subject catches a cold. These subjects will remain on stand-by and will be considered active participants until either the subject expresses an unwillingness to be involved in the study or the investigators obtain sufficient data to complete the study.
Intervention code [1] 290352 0
Early detection / Screening
Comparator / control treatment
Healthy persons 6 - 75 years.
Control group
Active

Outcomes
Primary outcome [1] 293280 0
To determine if individuals with poorly controlled allergic asthma who have persistent eosinophilic airway inflammation, also have impaired antiviral responses to RV. Characterised by impaired TLR7 signaling and increased CCL7 at baseline. These analyses will be determined using ELISA and FACscan.
Timepoint [1] 293280 0
Loss of asthma control (within the ICS withdrawal period (i.e. 8 weeks) for mild asthmatics; or within 6 months for the severe athma group; or, in healthy controls, the contraction of a cold during the 6 months following baseline assessment.
Secondary outcome [1] 310706 0
Nil
Timepoint [1] 310706 0
Nil

Eligibility
Key inclusion criteria
Participants:
This is a prospective case control study; we will recruit the following subjects:
1. Stable allergic asthma. Subjects aged 6 – 75 years with mild-to-moderate asthma (control of asthma symptoms (Asthma control questionnaire (ACQ6) score <1.5), and who have evidence of AHR to hypertonic saline and allergic sensitization to common inhalant allergens. On less than 1000mcg/d beclomethasone equivalent.
2. Severe uncontrolled allergic asthma, suitable for Omalizumab. Participants with severe refractory asthma, 18 years and older who have persistent poor asthma control (ACQ6 >1.5) despite treatment with greater than 1000mcg/d beclomethasone equivalent per day and a history of an acute exacerbation in the last 12 months requiring systemic corticosteroids for 3 days or more, and who are suitable for commencement of treatment with omalizumab.
3. Healthy controls. Non-asthmatic subjects aged 6 – 75 years with normal lung function and no allergic sensitization.

Key inclusion criteria

Cases with severe allergic asthma
*Asthma diagnosis, and who have evidence of AHR to hypertonic saline or change in FEV1 following bronchodilator >12% and at least 200mls.
*Age: 18 years and older and determined to be suitable for omalizumab treatment
*Regular maintenance treatment with inhaled corticosteroid and long acting beta agonist (dose of ICS >1000mcg/d fluticasone or 1600mcg/d of budesonide)
*Evidence of atopy, defined by positive skin prick test or RAST.
*Total serum IgE >75 IU/ml
*Persistent poor symptom control (ACQ6 >1.5).
*Oral corticosteroid use of at least 10mg/d of prednisone for at least 6 weeks in the last 12 months.
*Current non-smoker with <10 pack year history of smoking

Cases with controlled mild to moderate allergic asthma
*Asthma diagnosis, and who have evidence of AHR to hypertonic saline or change in FEV1 following bronchodilator >12% and at least 200mls.
*Age 6 -75 years
*Regular maintenance treatment with inhaled corticosteroid (dose of ICS <1000mcg/d fluticasone or 1600mcg/d of budesonide)
*Evidence of atopy, defined by positive skin prick test or RAST.
*Good asthma symptom control (ACQ6 <1.5)
*Current non-smoker with <10 pack year history of smoking

Healthy controls
*Normal lung function; FEV1 >80% predicted, FER >70% predicted and no evidence of AHR to hypertonic saline or change in FEV1 following bronchodilator >12% and at least 200mls.
*Age 6 -75 years
*No previous history of chronic cardiac or respiratory disease
*Non-atopic, negative skin prick test or RAST
*Current non-smoker with <10 pack year history of smoking
Minimum age
6 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Acute exacerbation of asthma within the last 4 weeks that required a change in treatment
*History of a viral respiratory tract infection within the last 4 weeks.
*Current smoker or former smoker with >10 pack year history of smoking.
*Inability to understand or comply with the study requirements

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
A total of 50 participants distributed into 3 study goups will be sought. We will need 10 participants to be treated with Omalizumab to have 80% power to find a 0.4 unit difference in the mean level of TLR7 between the two groups at the 5% level of significance. This calculation assumes that the Standard Deviation (SD) of TLR7 is 0.3.
We will need 20 subjects with mild to moderate asthma to have 80% power to find a 0.4 unit difference in the mean level of TLR7 between the two groups at the 5% level of significance. This calculation assumes that the Standard Deviation (SD) of TLR7 is 0.3. We are planning a study of a continuous response variable from independent control and experimental subjects with 1 control(s) per experimental subject. In the three month period we would expect 50% of subjects to exacerbate. In a previous study the response within each subject group was normally distributed with standard deviation 0.4. If the true difference in the experimental and control means is 0.4, we will need to study 10 exacerbating subjects and 10 stable subjects to be able to reject the null hypothesis that the population means of the experimental and control groups are equal with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.017. We plan to recruit 20 subjects, this will be sufficient to determine our primary endpoint as defined. 20 healthy control subjects will be recruited to provide comparative data for the mild and severe asthma groups.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/10/2014
Actual
Date of last participant enrolment
Anticipated
31/03/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3032 0
John Hunter Hospital Royal Newcastle Centre - New Lambton

Funding & Sponsors
Funding source category [1] 290033 0
Government body
Name [1] 290033 0
National Health & Medical Research Council (NH&MRC)
Country [1] 290033 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
Department of Respiratory Medicine
John Hunter Hospital
Lookout Road
New Lambton NSW 2305
Australia
Country
Australia
Secondary sponsor category [1] 288724 0
None
Name [1] 288724 0
Nil
Address [1] 288724 0
Nil
Country [1] 288724 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291739 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 291739 0
Ethics committee country [1] 291739 0
Australia
Date submitted for ethics approval [1] 291739 0
Approval date [1] 291739 0
02/09/2014
Ethics approval number [1] 291739 0
14/07/16/3.01

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51814 0
Prof Peter Wark
Address 51814 0
Level 2 HMRI
John Hunter Hospital
Lookout Road
New Lambton NSW 2305
Country 51814 0
Australia
Phone 51814 0
+61 2 4042 0138
Fax 51814 0
+61 2 4042 0046
Email 51814 0
[email protected]
Contact person for public queries
Name 51815 0
Douglas Dorahy
Address 51815 0
Level 2 HMRI
John Hunter Hospital
Lookout Road
New Lambton NSW 2305
Country 51815 0
Australia
Phone 51815 0
+61 2 4042 0133
Fax 51815 0
+61 2 4042 0046
Email 51815 0
[email protected]
Contact person for scientific queries
Name 51816 0
Peter Wark
Address 51816 0
Level 2 HMRI
John Hunter Hospital
Lookout Road
New Lambton NSW 2305
Country 51816 0
Australia
Phone 51816 0
+61 2 4042 0138
Fax 51816 0
+61 2 4042 0046
Email 51816 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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