Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00046644 |
| Other study ID # |
1189 |
| Secondary ID |
R01HL071394 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
September 30, 2002 |
| Last updated |
April 16, 2014 |
| Start date |
June 2002 |
| Est. completion date |
May 2005 |
Study information
| Verified date |
April 2014 |
| Source |
Nemours Children's Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Federal Government |
| Study type |
Observational
|
Clinical Trial Summary
To elucidate the mechanisms underlying inter-patient variation in response to montelukast, a
drug for asthma.
Description:
BACKGROUND:
Asthma is a common disease caused by a complex interaction between genetic and environmental
factors. Asthma afflicts 17 million Americans. In 1999, more than 5000 persons died from
asthma. Given the significant mortality and morbidity associated with asthma, it is
important to continue to develop new strategies for intervention. Leukotriene antagonists
are thought to be the most innovative approach to asthma therapy in 20 years. Despite their
demonstrated efficacy, safety and popularity, the leukotriene antagonists are associated
with a significant degree of inter-patient variability in response, which can limit their
safety, efficacy and cost-effectiveness. Several polymorphisms in leukotriene pathway genes
can contribute to variability in response. The project will determine if polymorphisms in
genes encoding 5-lipoxygenase, leukotriene A4hydrolase, LTC4 synthase, multi-drug resistance
protein 1 (MRP1) and LT1 receptor proteins are determinants of response to montelukast
treatment.
The study is in response to an Request for Applications entitled Ancillary Studies in Heart,
Lung, and Blood Disease Trials which was released by the NHLBI in June 2000 to conduct
mechanistic studies in clinical trials related to heart, lung and blood diseases.
Specifically, this initiative focuses on the utilization of patients and patient materials
from such trials to study the mechanisms underlying the interventions, the mechanisms of
disease pathogenesis, surrogate markers or biomarkers of disease activity and therapeutic
effect and the mechanisms of human cardiopulmonary and hematologic function. Studies aimed
at accelerating the development of new technologies within the context of the mechanistic
investigations are also encouraged.
DESIGN NARRATIVE:
DNA will be collected from patients participating in a parent clinical trial entitled:
Effectiveness of Low Dose Theophylline as Add-On Therapy in the Treatment of Asthma (LoDo
Trial). 627 patients from 19 Asthma Clinical Research Centers will be randomly assigned to
receive placebo, or low dose theophylline (300 mg/day) or montelukast, 10 mg daily, for 6
months. Stepwise Linear and Poisson regressions will be performed on outcomes including
treatment and genetic covariates, and interaction terms between treatment arm and genetic
makeup. Polymorphisms that are highly associated with response can lead to the development
of genetic tests that will identify patients most likely to benefit from montelukast
treatment. This information may lead to individualization of asthma medications based on the
genetic make-up of the patient.
