Asthma
Conditions
Keywords
Inhaled corticosteroids, Asthma, Pharmacogenomics, Genome wide association study, Admixture mapping, Continental population groups
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.
Interventions
DRUGbeclomethasone dipropionate
160 mcg twice a day (320 mcg per day total)
Sponsors
Henry Ford Health System
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Discovery set for ICS treatment response biomarker analysis
Eligibility
Sex/Gender
ALL
Age
12 Years to 56 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Asthma Control Test Score | 6 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
362 self-reported African American enrolled in 6-week treatment with inhaled beclomethasone dipropionate; 291 returned at the end of treatment; 262 with measurable medication adherence; 244 with genome-wide genotype data.
Participants by arm
| Arm | Count |
|---|---|
| Beclomethasone Dipropionate (BD) 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.
beclomethasone dipropionate: 160 mcg twice a day (320 mcg per day total) | 362 |
| Total | 362 |
Baseline characteristics
| Characteristic | Beclomethasone Dipropionate (BD) |
|---|---|
| Age, Continuous | 32.2 years STANDARD_DEVIATION 13 |
| Body Mass Index | 32.4 kilograms per meters squared STANDARD_DEVIATION 9.5 |
| Initial Asthma Control Test Score | 17.8 Composite Score STANDARD_DEVIATION 5 |
| Percent of Predicted Forced Expiratory Volume at 1 Second | 73.0 % of the predicted FEV1 STANDARD_DEVIATION 12.6 |
| Proportion of African Genetic Ancestry | 80.6 % African Ancestry (within individuals) STANDARD_DEVIATION 8.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 362 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 216 Participants |
| Sex: Female, Male Male | 146 Participants |
| Smoking Status Current Smoker | 3 Participants |
| Smoking Status Never Smoker | 315 Participants |
| Smoking Status Past Smoker | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 362 |
| other Total, other adverse events | 0 / 362 |
| serious Total, serious adverse events | 0 / 362 |
Outcome results
Primary
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.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Beclomethasone Dipropionate (BD) | Change in Asthma Control Test Score | 3.32 change in composite score | Standard Deviation 4.47 |