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Trial registered on ANZCTR


Registration number
ACTRN12608000393358
Ethics application status
Approved
Date submitted
24/07/2008
Date registered
4/08/2008
Date last updated
3/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Intal and Singulair, alone and in combination in asthma provoked by inhalation of a sugar.
Scientific title
The effect of sodium cromoglycate alone, and in combination with montelukast sodium, on the airway sensitivity and recovery from challenge with inhaled mannitol in subjects with asthma.
Secondary ID [1] 660 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
asthma 3461 0
Condition category
Condition code
Respiratory 3621 3621 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study consisted of 4 visits of approximately 1.5 hours and each visit was scheduled to take place at the same time of day. There was a minimum of 2 days between study days 1 & 2 and a minimum of 4 days with a maximum of 2 weeks between study days 2-4. The minimum time in which a study was completed was 11 days, the maximum was 26 days, with an average of 16 days taken to complete a study.

Day 1: Subjects with a measured forced expiratory volume in one second (FEV1) of at least 70% predicted received a challenge with inhaled mannitol. The challenge ceased when a fall of 20% in FEV1 was achieved or 635 mg of mannitol was administered through a dry power inhaler (Osmohaler™). Subjects who recorded the 20% fall in FEV1 following the delivery of up to 315 mg were enrolled in the study. They were given a randomisation number that determined the order of administration of either placebo sodium cromoglycate (SCG) & placebo montelukast sodium (MS), SCG & placebo MS, or SCG & MS. They were given a vial containing two tablets of either montelukast sodium (10 mg) or its placebo. They were asked to take one tablet on the evening prior to their next study day, and a second tablet 3-5 hours prior to the study.

On arrival at the laboratory on the subsequent study days FEV1 was measured in triplicate then SCG (2 x 20 mg) or a placebo administered by inhalation through a dry powder inhaler (Inhalator™). FEV1 was measured after 15 minutes then a challenge with mannitol followed, with the administration of the same dose that caused a 20% fall in FEV1 on the first day. Subjects recovered from challenge spontaneously, and FEV1 was measured at 5 minutes and then every 10 minutes until 30 minutes. If the FEV1 had not recovered to within 5% of baseline FEV1, 2 puffs (200 mcg) of salbutamol was administered and FEV1 monitored until it had recovered.
Duration of interventions:
SCG - one hour
MS - 14 hours
Intervention code [1] 3190 0
Prevention
Intervention code [2] 3191 0
Treatment: Drugs
Comparator / control treatment
The placebos used for SCG and MS were supplied by Ciba Geigy (001000 foradile placebo) and Merck, Sharp & Dohme (MS placebo CA-A608).
Control group
Placebo

Outcomes
Primary outcome [1] 4516 0
Response to challenge with mannitol as expressed by the maximum percent fall in FEV1 (forced expiratory volume in the first second) from the prechallenge value.
Timepoint [1] 4516 0
approximately 23 minutes after commencement of challenge (the usual length of a challenge using 635 mg)
Primary outcome [2] 4517 0
Area above the FEV1 (forced expiratory volume in the first second) time recovery curve to compare placebo, sodium cromoglycate, and sodium cromoglycate/montelukast sodium
Timepoint [2] 4517 0
30 minutes after end of challenge
Secondary outcome [1] 7637 0
time of recovery to within 5% of recovery to pre challenge FEV1 (forced expiratory volume in the first second)
Timepoint [1] 7637 0
Recovery to within 5% of prechallenge FEV1 (forced expiratory volume in the first second) took place between 5 and 50 minutes of cessation of challenge.

Eligibility
Key inclusion criteria
Clinical diagnosis of asthma, FEV1 =70% Predicted; adherent to prescribed ICS (inhaled corticosteroid) therapy for past 4 weeks, no chest infection in last 4 weeks, able to withhold current asthma medication for required time
Minimum age
15 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
pregnant females or those at risk of becoming pregnant, those breast feeding, current smokers or those with a recent (< 1 yr) past history of smoking, known sensitivity to either sodium cromoglycate or montelukast sodium or their components, taking of oral corticosteroids in the last 4 weeks.

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)
When subjects met inclusion criteria they were given a number. The treatment had been packed in numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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 in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 1029 0
2037
Recruitment postcode(s) [2] 1030 0
2033
Recruitment postcode(s) [3] 1031 0
2144
Recruitment postcode(s) [4] 1032 0
2008
Recruitment postcode(s) [5] 1033 0
2049
Recruitment postcode(s) [6] 1034 0
2137
Recruitment postcode(s) [7] 1035 0
2747
Recruitment postcode(s) [8] 1036 0
2050
Recruitment postcode(s) [9] 1037 0
2219
Recruitment postcode(s) [10] 1038 0
2022
Recruitment postcode(s) [11] 1039 0
2042
Recruitment postcode(s) [12] 1040 0
2750

Funding & Sponsors
Funding source category [1] 3643 0
Government body
Name [1] 3643 0
NHMRC
Address [1] 3643 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 3643 0
Australia
Primary sponsor type
Individual
Name
Dr. Sandra D. Anderson
Address
Department of Respiratory & Sleep Medicine
11 West, Building 75
Royal Prince Alfred Hospital
Missenden Road, Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 3276 0
None
Name [1] 3276 0
Address [1] 3276 0
Country [1] 3276 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5698 0
Ethics Review Committee of Central Sydney Area Health Service
Ethics committee address [1] 5698 0
Research Development Office
Level 8, Building 14
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [1] 5698 0
Australia
Date submitted for ethics approval [1] 5698 0
15/11/2004
Approval date [1] 5698 0
20/12/2004
Ethics approval number [1] 5698 0
X04-0276

Summary
Brief summary
The protection provided by sodium cromoglycate, against airway narrowing provoked by mannitol, is incomplete. This is likely due to the failure of SCG to prevent release of leukotrienes from cells other than mast cells. The protection against airway narrowing in response to mannitol will be more complete using a combination of SCG and a leukotriene antagonist.
Trial website
Trial related presentations / publications
The effect of montelukast sodium in additon to sodium cromoglycate (SCG) on the airway response to the same cumulative dose of inhaled mannitol (Abstract) European Respiratory Journal 2005 Annual Scientific Meeting (September Supplement)
Public notes

Contacts
Principal investigator
Name 28781 0
Address 28781 0
Country 28781 0
Phone 28781 0
Fax 28781 0
Email 28781 0
Contact person for public queries
Name 11938 0
Clare Perry
Address 11938 0
Department of Respiratory & Sleep Medicine
11 West, Building 75
Royal Prince Alfred Hospital
Missenden Road, Camperdown NSW 2050
Country 11938 0
Australia
Phone 11938 0
02 9515 6121
Fax 11938 0
02 9515 8196
Email 11938 0
clarep@med.usyd.edu.au
Contact person for scientific queries
Name 2866 0
Dr Sandra D. Anderson
Address 2866 0
Department of Respiratory & Sleep Medicine
11 West, Building 75
Royal Prince Alfred Hospital
Missenden Road, Camperdown NSW 2050
Country 2866 0
Australia
Phone 2866 0
02 9515 6120
Fax 2866 0
02 9515 8196
Email 2866 0
sandya@med.usyd.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary