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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| beclomethasone dipropionate (BD) | Other | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| beclomethasone dipropionate | Drug | 160 mcg twice a day (320 mcg per day total) |
|
| 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 |
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Inclusion Criteria for Discovery Group:
Exclusion Criteria for Discovery Group:
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| Name | Affiliation | Role |
|---|---|---|
| L. Keoki Williams, MD, MPH | Henry Ford Health System | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Henry Ford Health System | Detroit | Michigan | 48202 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30367910 | Result | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Beclomethasone Dipropionate (BD) | Patients who meet eligibility criteria will be treated with 6 weeks of beclomethasone dipropionate to assess change in asthma control. This change will be the phenotype used in discovery for the genetic association study. There is no placebo group. beclomethasone dipropionate: 160 mcg twice a day (320 mcg per day total) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | change in composite score | 6 weeks |
|
6 weeks of treatment with inhaled beclomethasone dipropionate.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Beclomethasone Dipropionate (BD) | Patients who meet eligibility criteria will be treated with 6 weeks of beclomethasone dipropionate to assess change in asthma control. This change will be the phenotype used in discovery for the genetic association study. There is no placebo group. beclomethasone dipropionate: 160 mcg twice a day (320 mcg per day total) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| L. Keoki Williams, MD, MPH | Center for Individualized and Genomic Medicine Research, Henry Ford Health System | 313-874-5454 | kwillia5@hfhs.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 19, 2016 | Feb 19, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D001507 | Beclomethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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Discovery set for ICS treatment response biomarker analysis
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| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Proportion of African Genetic Ancestry | Some individuals did not have the genome wide genotype data needed to assess genetic ancestry. | Mean | Standard Deviation | % African Ancestry (within individuals) |
|
| Body Mass Index | Mean | Standard Deviation | kilograms per meters squared |
|
| Smoking Status | Smoking status missing on seven individuals | Count of Participants | Participants |
|
| Initial Asthma Control Test Score | The Asthma Control Test comprises five questions, each with a Likert Scale of 1 to 5. Therefore, the composite score for an individual ranges from 5 to 25. Higher composite scores denote better controlled asthma. | Initial ACT score missing in 8 individuals | Mean | Standard Deviation | Composite Score |
|
| Percent of Predicted Forced Expiratory Volume at 1 Second | The predicted forced expiratory volume at one second (FEV1) is derived from predictive equations derived from population based studies (Hankinson et al. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87.). The percent of predicted for an individual is derived by dividing the measured FEV1 for that individual by their predicted measure (the later is based on an individual's age, sex, and race-ethnicity). | Mean | Standard Deviation | % of the predicted FEV1 |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| 0 |
| 362 |
| 0 |
| 362 |
| 0 |
| 362 |
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013258 | Steroids, Chlorinated |