Leukotriene Polymorphisms and Montelukast Response - Ancillary to LoDo Trial

This study has been completed.
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:
Nemours Children's Clinic
ClinicalTrials.gov Identifier:
First received: September 30, 2002
Last updated: April 16, 2014
Last verified: April 2014
To elucidate the mechanisms underlying inter-patient variation in response to montelukast, a drug for asthma.

Lung Diseases

Study Type: Observational

Further study details as provided by Nemours Children's Clinic:

Study Start Date: June 2002
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Detailed Description:


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.


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.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
No eligibility criteria
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00046644

Sponsors and Collaborators
Nemours Children's Clinic
National Heart, Lung, and Blood Institute (NHLBI)
OverallOfficial: John Lima Nemours Children's Clinic
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00046644     History of Changes
Other Study ID Numbers: 1189  R01HL071394 
Study First Received: September 30, 2002
Last Updated: April 16, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on May 26, 2016