Clinical trial NCT01142947: Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE)
Official title: Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: Inhaled corticosteroids
Asthma
Pharmacogenomics
Genome wide association study
Admixture mapping
Continental population groups
Lead sponsor: Henry Ford Health System
Sponsor class: OTHER
First posted: 2010-06-14
Enrollment: 362
Sex: ALL
Minimum age (years): 12
Maximum age (years): 56
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Discovery set for ICS treatment response biomarker analysis
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Change in Asthma Control Test Score
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
Study officials:
affiliation: Henry Ford Health System
name: L. Keoki Williams, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Levin AM, Gui H, Hernandez-Pacheco N, Yang M, Xiao S, Yang JJ, Hochstadt S, Barczak AJ, Eckalbar WL, Rynkowski D, Samedy LA, Kwok PY, Pino-Yanes M, Erle DJ, Lanfear DE, Burchard EG, Williams LK. Integrative approach identifies corticosteroid response variant in diverse populations with asthma. J Allergy Clin Immunol. 2019 May;143(5):1791-1802. doi: 10.1016/j.jaci.2018.09.034. Epub 2018 Oct 24.