Clinical trial NCT00831376: Trough Bronchoprotection Conferred by Levosalbutamol and Racemic Salbutamol
Official title: A Proof of Concept Study to Evaluate the Trough Bronchoprotection Conferred by Chronic Dosing With Levosalbutamol and Racemic Salbutamol in Persistent Asthmatics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Asthma
Genotype
Beta2adrenoreceptor
Levosalbutamol
Lead sponsor: University of Dundee
Sponsor class: OTHER
First posted: 2009-01-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The objective of this study is to compare the relative bronchoprotection (at trough) conferred by 2-week chronic dosing with levosalbutamol and racemic salbutamol in mild to moderate asthmatics. Patients will be preselected into two groups on the basis of their beta-2 adrenoreceptor polymorphisms. The investigators will evaluate if this has a differential effect on the bronchoprotection conferred by both formulations of salbutamol, as evidenced by a rebound in airway hyper-responsiveness, in order to determine whether any effect can be explained by the S enantiomer in the racemic formulation.


Eligibility criteria: Inclusion Criteria:

1. Mild to moderate stable asthmatics on ≤ 2000μg BDP or equivalent, who are methacholine responsive PC20\< 4 mg/ml
2. \>1dd change in methacholine PC20 after the administration of racemic Salbutamol.
3. Male or female 18-65
4. Informed Consent
5. Ability to comply with the requirements of the protocol

Exclusion Criteria:

1. Severe asthmatics as defined by an FEV1≤ 60% or PEF variability \> 30% or with continual daytime or nocturnal symptoms.
2. The use of oral corticosteroids within the last 3 months.
3. Recent respiratory tract infection (2 months).
4. Significant concomitant respiratory disease such as COPD, CF, ABPA, bronchiectasis and active pulmonary tuberculosis.
5. Any other clinically significant medical condition such as unstable angina, acute myocardial infarction in the preceding 3 months, recent TIA/ CVA, that may endanger the health or safety of the participant, or jeopardise the protocol.
6. Any significant abnormal laboratory result as deemed by the investigators
7. Pregnancy, planned pregnancy or lactation
8. Known or suspected contra-indication to any of the IMP's
9. Concomitant use of medicines (prescribed, over the counter or herbal) that may interfere with the trial.

Primary outcomes:
measure: methacholine challenge
timeFrame: before and after 2 week study period
Secondary outcomes:
measure: spirometry
timeFrame: before and after 2 week study period
measure: nitric oxide levels
timeFrame: before and after 2 week study period
measure: symptom scores
timeFrame: before and after 2 week study period
measure: Bmax and Emax
timeFrame: before and after 2 week study period
Other outcomes:
Locations:
city: Dundee
country: United Kingdom
facility: Asthma and Allergy Research Group
state: Angus
Study officials:
affiliation: Asthma and Allergy Research Group
name: Karine L Clearie, MBBS, MRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: Asthma and Allergy Research Group
name: Brian J Lipworth, MBchB
role: STUDY_DIRECTOR
References:
citation: Anderson WJ, Short PM, Williamson PA, Morrison AE, Palmer C, Tavendale R, Lipworth BJ. Proof-of-concept evaluation of trough airway hyper-responsiveness following regular racemic or levosalbutamol in genotype-stratified steroid-treated persistent asthmatic patients. Clin Sci (Lond). 2014 Jan 1;126(1):75-83. doi: 10.1042/CS20130213.