Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE)

Study Overview
=================
Brief Summary
-----------------
Inhaled corticosteroids (ICS) are considered first-line treatment for persistent asthma, yet little is known about the genetic factors that influence response to this therapy. This study seeks to quantify response to ICS therapy in African American and white patients, as well as look for genetic markers that predict treatment response.

Detailed Description
-----------------
Inhaled corticosteroids (ICS) are considered first-line therapy for the management and control of patients with persistent asthma. Use of inhaled steroids has been associated with improved lung function, diminished symptoms, and fewer exacerbations. However studies show considerable inter-subject variability in ICS response. It has also been estimated that corticosteroid resistance accounts for half of all asthma-related health care costs. Therefore, identifying factors associated with ICS response is both clinical and economically important. African-American patients have been understudied with respect to genetic predictors of asthma controller medication response, and to date there have been no sufficiently powered genome-wide association studies of ICS treatment response among African American individuals with asthma. This issue is of particular importance, since African-American individuals are disproportionately affected by asthma-related complications. In this proposal, we seek to identify novel genetic loci associated with ICS treatment responsiveness (defined by the change in Asthma Control Test score) among African American individuals treated with beclomethasone dipropionate (BD) for 6 weeks. We will attempt to validate loci identified in the discovery set by 1) reassessing these variants for their interaction with ICS treatment on asthma exacerbations in a separate group of African American individuals with asthma, and 2) by reexamining the genetic association with change in asthma control among similarly treated (i.e., treatment with 6 weeks of BD) European Americans with asthma.

Official Title
-----------------
Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE)

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: beclomethasone dipropionate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria for Discovery Group: Age 12-56 years Physician diagnosis of asthma (identified by using encounter data prior to screening and by the survey administered at the clinic visit) Bronchodilator reversibility on pulmonary function testing (i.e., improvement in baseline FEV1 of >12%) African-American/Black self-reported race-ethnicity Exclusion Criteria for Discovery Group: Smoking in the preceding year or <10 pack-year smoking history total Pregnant at the time of enrollment or intending to get pregnant during the 6-week treatment period Oral or inhaled corticosteroid use in the 4 weeks preceding enrollment Prior diagnosis of chronic obstructive pulmonary disease or emphysema Prior diagnosis of congestive heart failure Self-reported race not African-American/Black or Hispanic ethnicity (these groups could be included in Replication/Validation group)

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 56 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Discovery set for ICS treatment response biomarker analysis
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: beclomethasone dipropionate (BD)<br>Patients who meet eligibility criteria will be treated with 6 weeks of beclomethasone dipropionate to assess change in pulmonary function and asthma control. These change will be used as phenotypes in a genetic association study. There is no placebo group. | Drug: beclomethasone dipropionate<br>* 160 mcg twice a day (320 mcg per day total)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Asthma Control Test Score | Patients will be treated with 6 weeks of inhaled beclomethasone diproprionate (BD) treatment and the change in Asthma Control Test (ACT) quantified. The composite ACT score measured at each time point ranged from 5-25 (with higher scores reflective of better asthma control). Therefore, the absolute change in ACT score from before to after treatment could range from -20 to +20. | 6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inhaled corticosteroids, Asthma, Pharmacogenomics, Genome wide association study, Admixture mapping, Continental population groups