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Trial registered on ANZCTR


Registration number
ACTRN12615001166561
Ethics application status
Approved
Date submitted
19/10/2015
Date registered
2/11/2015
Date last updated
20/08/2019
Date data sharing statement initially provided
1/11/2018
Date results information initially provided
1/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of the efficacy of a carrageenan nasal spray when taken during a cold in reducing asthma exacerbations as measured by the asthma control questionnaire.
Scientific title
A randomised placebo controlled trial of the efficacy of carrageenan nasal spray in reducing asthma exacerbations, as measured by the asthma control questionnaire, when taken during a cold.
Secondary ID [1] 287603 0
None
Universal Trial Number (UTN)
U1111-1175-2023
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma exacerbation during a cold 296407 0
Colds 296408 0
Condition category
Condition code
Respiratory 296674 296674 0 0
Asthma
Infection 296675 296675 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A nasal spray containing saline solution and 1.6 mg/ml carrageenan will be taken by participants in the active group during a cold. Each spray contains 0.14ml of the solution..

Participants will spray each nostril 4 times per day (first thing in the morning, at lunch time, at dinner time and before bed) for 10 days at the start of cold symptoms. Participants will fill in an asthma control questionnaire (ACQ) at baseline with no cold, and on day 7 and day 14 of a cold. From the start of a cold, cold symptoms and peak flow will be recorded daily for 14 days, and for a further 7 days if cold symptoms persist. Nasal swabs will be taken to establish virus type and viral positive colds on day 2 and day 10, and a further swab will be taken on day 18 if cold symptoms persist. Participants will be followed for 16 weeks between April and November (peak cold season), and will treat up to two colds using the spray during this time, if they experience cold symptoms. Nasal spray bottle weights will be measured to determine compliance. Participants will be skin prick tested to common environmental allergens (house dust mite, cat, mixed grasses) to establish their atopic status.
Intervention code [1] 292999 0
Treatment: Other
Comparator / control treatment
A nasal spray containing saline solution will be taken by participants in the placebo group during a cold. Participants will spray each nostril 4 times per day for 10 days at the start of cold symptoms.

Methodology for the placebo group will be the same as the the protocol for the active group (outlined in the intervention/exposure* section above).
Control group
Placebo

Outcomes
Primary outcome [1] 296280 0
The primary outcome measure will be the difference from baseline in ACQ scores with a cold between the placebo and active groups.
Timepoint [1] 296280 0
After 7 days of having a cold (ACQ score in past 7 days).
Secondary outcome [1] 318045 0
Bronchodilator medication use between the active and placebo groups. This will be measured by self-reporting in the symptoms diaries.
Timepoint [1] 318045 0
In the 14 days following the start of cold symptoms.
Secondary outcome [2] 318046 0
Percentage reduction from baseline in respiratory peak flow between active and placebo during a cold. Daily peak flow meter readings as recorded in symptom diaries. These measures will be compared to the baseline peak flow reading taken at the enrolment visit when they do not have a cold.
Timepoint [2] 318046 0
Average over 14 days from the start of a cold.
Secondary outcome [3] 318047 0
Number of days with cold symptoms between the active group and the placebo group. These will be self-reported cold symptoms as recorded in the symptom diary.
Timepoint [3] 318047 0
In the 14 days following the start of cold symptoms.
Secondary outcome [4] 318049 0
Severity of cold symptoms between the active group and the placebo group. The severity cold symptoms is measured by taking the total score for each symptom over the duration of a cold and dividing it by the total number of days of a cold.
Timepoint [4] 318049 0
In the 14 days following the start of cold symptoms.
Secondary outcome [5] 318050 0
Average level of rhinovirus in nose on day 2 and day 10 of a cold between the active group and the placebo group. Rhinovirus levels will be measured by quantitative polymerase chain reaction (qPCR) assays.
Timepoint [5] 318050 0
Days 2 and days 10 of a cold.
Secondary outcome [6] 318318 0
ACQ at baseline and on day 7 for atopic and non-atopic asthmatics in the carrageenan group, and in the placebo group.
Timepoint [6] 318318 0
Day 7 from the start of a cold.
Secondary outcome [7] 318319 0
The proportion of viral positive nasal swabs taken on day 10 of a cold will be compared between atopic and non-atopic individuals in the carrageenan and the placebo group.
Timepoint [7] 318319 0
Nasal swabs for viral analysis will be taken on Day 10 after the start of a cold..
Secondary outcome [8] 318320 0
Self-reported GP, after hours medical centre or hospital A&E visits for asthma.
Timepoint [8] 318320 0
At the end of each cold, we will ask participants if they had needed to see their GP, after hours medical centre or hospital A&E Department for asthma during the cold.

Eligibility
Key inclusion criteria
People who have ever been doctor diagnosed with asthma, and who have had at least one cold in the past 12 months with asthma symptoms.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Those with COPD (doctor diagnosed), those who plan to use a nasal spray for another condition during the study period, those whose asthma does not worsen with a cold, those who have a previous sensitivity or allergy to carrageenan or other seaweed products, a history of nasal polyps, or those with 'current unstable asthma' which we define as having been hospitalised for asthma within the last 2 months or use of oral corticosteroids in the past month.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment of bottles between placebo and active will occur by the manufacturer, off-site, who will use central randomisation by computer to allocate bottle codes. Researchers will use the next available bottle number, and are blinded to allocation throughout the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation by computer. Two lists will be generated, and those who've had an emergency visit for asthma in the past 12 months will be assigned to one list, and all other asthmatics to another. This is to distrubute those few participants with severe asthma evenly between the active and placebo groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Assuming 75% of participants in our proposed study will develop cold symptoms during the 16 weeks of participation, then 150 subjects in each group will have 82.8% power to detect a reduction in ACQ of 0.34 with a cold. Assuming a dropout rate of 15% we will recruit 360 participants into the study (180 in each group). The primary analysis will use a hierarchical linear model with individual as the lower level and the size of the increase in ACQ.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7206 0
New Zealand
State/province [1] 7206 0
Wellington

Funding & Sponsors
Funding source category [1] 292167 0
Government body
Name [1] 292167 0
Health Research Council of New Zealand
Address [1] 292167 0
Level 3, Pro CARE Building, Grafton Mews
110 Stanley Street
Auckland 1010
Country [1] 292167 0
New Zealand
Primary sponsor type
Individual
Name
Julian Crane
Address
University of Otago, Wellington
23a Mein Street
Newtown
Wellington 6021
Country
New Zealand
Secondary sponsor category [1] 290840 0
None
Name [1] 290840 0
Address [1] 290840 0
Country [1] 290840 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293639 0
Central Regional Ethics Committee
Ethics committee address [1] 293639 0
Ministry of Health
No.1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 293639 0
New Zealand
Date submitted for ethics approval [1] 293639 0
12/11/2015
Approval date [1] 293639 0
02/02/2016
Ethics approval number [1] 293639 0

Summary
Brief summary
New Zealand has high rates of asthma and hospitalisations for asthma. Viral respiratory infections are the most common cause of asthma exacerbations in both children and adults. Preliminary laboratory and clinical evidence points to carrageenan nasal spray (an extract of red seaweed) being a potentially exciting new treatment for cold virus infections. This study will investigate how effective using a nasal spray containing carrageenan is as a treatment against the development of asthma exacerbations caused by cold infections, in adults with asthma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60806 0
Prof Julian Crane
Address 60806 0
Department of Medicine
University of Otago Wellington
23a Mein Street
Newtown
Wellington 6021
Country 60806 0
New Zealand
Phone 60806 0
+64 4 918 5258
Fax 60806 0
Email 60806 0
julian.crane@otago.ac.nz
Contact person for public queries
Name 60807 0
Prof Julian Crane
Address 60807 0
Department of Medicine
University of Otago Wellington
23a Mein Street
Newtown
Wellington 6021
Country 60807 0
New Zealand
Phone 60807 0
+64 4 918 5258
Fax 60807 0
Email 60807 0
julian.crane@otago.ac.nz
Contact person for scientific queries
Name 60808 0
Prof Julian Crane
Address 60808 0
Department of Medicine
University of Otago Wellington
23a Mein Street
Newtown
Wellington 6021
Country 60808 0
New Zealand
Phone 60808 0
+64 4 918 5258
Fax 60808 0
Email 60808 0
julian.crane@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We did not recieve consent from participants to do this, which would be an ethical requirement.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary