Asthma in ChildrenSTARNCT03134755
Stress and Treatment Response in Puerto Rican Children With Asthma
An observational study of Asthma in Children, run by University of Pittsburgh at 2 sites in 2 countries.
Trial summary
This study aims to first determine whether high child stress leads to reduced response to common treatmenIs for asthma (inhaled corticosteroids and short-acting bronchodilators), and then to identify DNA methylation differences leading to stress-induced treatment resistance among children with asthma. Read more about this study
- Who is it for?
- Ages 8 to 20 years
- Conditions the study is for
- Asthma in Children
- What is being tested?
- Inhaled corticosteroid (mometasone)
- How many people
- 249 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 15 May 2018to 18 May 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: 300 Puerto Rican and African American children with mild to moderate persistent asthma, ages 8 to 20 years. Of these children, 150 (all Puerto Rican) will be recruited in the metropolitan area of San Juan and Caguas (Puerto Rico), and 150 (all African American) will be recruited in Pittsburgh (PA).
Who may be able to join
- Physician-diagnosed asthma
- BDR ≥8%99 or (if BDR<8%) increased airway responsiveness to methacholine (PD20 <16.81 umol)
- Four Puerto Rican grandparents
- Steroid naïve (no treatment with ICS, nasal, or oral corticosteroids in the prior 4 weeks)
- Parental consent and child's assent to participate in the study
Who cannot join
- Chronic disease (i.e. respiratory, liver, cardiac, renal, neurologic) other than asthma
- Severe asthma, as evidenced by: a) intubation for asthma at any time, or b) ≥3 hospitalizations or ≥6 visits to the emergency department/urgent care in the previous year, or c) chronic/continuous need for medications other than single controller therapy [ICS or leukotriene inhibitors] and short-acting β2-agonists
- Current smoking or former smoking if ≥5 pack-years
- Inability to perform acceptable spirometry
- FEV1 <60% of predicted
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Puerto Rico1 site
Behavioral Sciences Research Institute, University of Puerto Rico
San Juan, PR, 00936
About this study
This study aims to first determine whether high child stress leads to reduced response to common treatmenIs for asthma (inhaled corticosteroids and short-acting bronchodilators), and then to identify DNA methylation differences leading to stress-induced treatment resistance among children with asthma.
Read the detailed description
Puerto Rican (PR) and African American children share a disproportionate burden from asthma in the U.S. The investigators have demonstrated that in PR children, a variety of psychological stressors are associated with worse asthma outcomes. Puerto Rican children also have reduced response to bronchodilators (short-acting inhaled β2-agonists, the most commonly used medication for asthma worldwide). The investigators have recently shown that high child stress is associated with reduced response to short-acting inhaled β2-agonists (bronchodilator response or BDR) in PR and non-PR children with asthma, and our preliminary results also implicate genetic and epigenetic (DNA methylation) variation in genes involved in stress responses (e.g., ADCYAP1R1) on asthma and BDR. Moreover, external in vitro experiments show that high stress leads to reduced expression of the genes for the β2-adrenergic receptor (ADRB2) and the glucocorticoid receptor (NR3C1) in white blood cells of children with asthma. While it is known that stress reduces BDR, it is not known whether this can be prevented by treatment with inhaled corticosteroids (ICS), or whether stress reduces response to ICS in vivo. Moreover, the research community has very limited knowledge of the genetic or epigenetic mechanisms underlying treatment resistance in stressed children. On the basis of novel preliminary results, the investigators hypothesize that chronic stress reduces response to inhaled corticosteroids (ICS) and BDR in PR and African American children with asthma, and that these effects are mediated by altered methylation of genes regulating responses to stress, corticosteroids and BDR. To test this hypothesis, the investigators will first determine whether increased stress leads to reduced response to ICS or BDR (even after treatment with ICS) in 300 PR and African American children with asthma (Aim 1). The investigators will then test for association between high child stress and genome-wide DNA methylation in respiratory (nasal) epithelium in 550 Puerto Rican and African American children with asthma (Aim 2). Next, the investigators will examine whether methylation changes in the top 100 genes identified in Aim 2 are associated with response to ICS or BDR in 300 to 550 PR and African American children with asthma (Aim 3a). Finally, the investigators will assess the effects of methylation changes identified in Aim 3a on gene expression (Aim 3b). This proposal should determine whether and how psychosocial stress leads to reduced response to common treatments for asthma control (ICS) and relief of asthma symptoms (short-acting inhaled β2-agonists) in a high-risk group (Puerto Rican and African American children).
- Conditions
- Asthma in Children
- Being tested
- Inhaled corticosteroid (mometasone)
- Keywords
- Asthma, Children, Stress, Puerto Rican, Health disparities, Treatment response, African American
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled corticosteroid (mometasone)Drug
Also called Asmanex
The investigators are not measuring the effect of the intervention (ICS), but rather the effect of stress (which is not being intervened on), and this is thus an observational study. The ICS is given to children with asthma in whom an ICS is clinically indicated
| Study group | Role | What they receive |
|---|---|---|
| Study cohort (all children with asthma) | 300 children with asthma will receive the same inhaled corticosteroid (ICS) for six weeks, in order to assess response to ICS.Bronchodilator response will be measured before and after ICS therapy. Stress levels (the exposure of interest) will be assessed with a validated questionnaire, before ICS administration (thus, it is an observational study of whether stress is related to treatment response) Receives: Drug: Inhaled corticosteroid (mometasone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bronchodilator response (BDR)
BDR will be measured as the change in forced expiratory volume in 1 second (FEV1) after administration of a short-acting bronchodilator (albuterol)
Measured: 15 minutes
Response to inhaled corticosteroids (ICS)
ICS response will be measured as change in forced expiratory volume in 1 second (FEV1) and as change in the xhild-Asthma Control Test (C-ACT) score, following six weeks of ICS administration
Measured: Six weeks
DNA methylation and gene expression differences
The investigators will examine whether child stress is associated with DNA methylation or gene expression differences, and such differences will then be tested for association with BDR or ICS response (measured as above)
Measured: Six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2017
- Study start15 May 2018
- Primary completion18 May 2022
- Study completion18 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asthma in ChildrenStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 249 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Juan Celedon, MD, University of Pittsburgh
- Investigators
- Juan C Celedon, MD, DrPH, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03134755
- Sponsor's protocol ID
- PRO17030493
- Other IDs
- R01HL117191
- Acronym
- STAR
- Status last verified
- Feb 2025
- First submitted
- 26 Apr 2017
- Last updated
- 11 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stress and Treatment Response in Puerto Rican Children With Asthma
- ClinicalTrials.gov ID
- NCT03134755
- Acronym / sponsor ID
- STAR / PRO17030493
- Conditions
- Asthma in Children
- Keywords
- Asthma, Children, Stress, Puerto Rican, Health disparities, Treatment response, African American
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 249 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 15 May 2018 (actual)
- Primary completion
- 18 May 2022 (actual)
- Study completion
- 18 May 2022 (actual)
- First posted
- 1 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to first determine whether high child stress leads to reduced response to common treatmenIs for asthma (inhaled corticosteroids and short-acting bronchodilators), and then to identify DNA methylation differences leading to stress-induced treatment resistance among children with asthma.
Detailed description
Puerto Rican (PR) and African American children share a disproportionate burden from asthma in the U.S. The investigators have demonstrated that in PR children, a variety of psychological stressors are associated with worse asthma outcomes. Puerto Rican children also have reduced response to bronchodilators (short-acting inhaled β2-agonists, the most commonly used medication for asthma worldwide). The investigators have recently shown that high child stress is associated with reduced response to short-acting inhaled β2-agonists (bronchodilator response or BDR) in PR and non-PR children with asthma, and our preliminary results also implicate genetic and epigenetic (DNA methylation) variation in genes involved in stress responses (e.g., ADCYAP1R1) on asthma and BDR. Moreover, external in vitro experiments show that high stress leads to reduced expression of the genes for the β2-adrenergic receptor (ADRB2) and the glucocorticoid receptor (NR3C1) in white blood cells of children with asthma. While it is known that stress reduces BDR, it is not known whether this can be prevented by treatment with inhaled corticosteroids (ICS), or whether stress reduces response to ICS in vivo. Moreover, the research community has very limited knowledge of the genetic or epigenetic mechanisms underlying treatment resistance in stressed children. On the basis of novel preliminary results, the investigators hypothesize that chronic stress reduces response to inhaled corticosteroids (ICS) and BDR in PR and African American children with asthma, and that these effects are mediated by altered methylation of genes regulating responses to stress, corticosteroids and BDR. To test this hypothesis, the investigators will first determine whether increased stress leads to reduced response to ICS or BDR (even after treatment with ICS) in 300 PR and African American children with asthma (Aim 1). The investigators will then test for association between high child stress and genome-wide DNA methylation in respiratory (nasal) epithelium in 550 Puerto Rican and African American children with asthma (Aim 2). Next, the investigators will examine whether methylation changes in the top 100 genes identified in Aim 2 are associated with response to ICS or BDR in 300 to 550 PR and African American children with asthma (Aim 3a). Finally, the investigators will assess the effects of methylation changes identified in Aim 3a on gene expression (Aim 3b). This proposal should determine whether and how psychosocial stress leads to reduced response to common treatments for asthma control (ICS) and relief of asthma symptoms (short-acting inhaled β2-agonists) in a high-risk group (Puerto Rican and African American children).
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study cohort (all children with asthma) | – | Drug: Inhaled corticosteroid (mometasone)300 children with asthma will receive the same inhaled corticosteroid (ICS) for six weeks, in order to assess response to ICS.Bronchodilator response will be measured before and after ICS therapy. Stress levels (the exposure of interest) will be assessed with a validated questionnaire, before ICS administration (thus, it is an observational study of whether stress is related to treatment response) |
Who may qualify
- Ages
- 8 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- 300 Puerto Rican and African American children with mild to moderate persistent asthma, ages 8 to 20 years. Of these children, 150 (all Puerto Rican) will be recruited in the metropolitan area of San Juan and Caguas (Puerto Rico), and 150 (all African American) will be recruited in Pittsburgh (PA).
Key inclusion criteria (5 listed)
- Physician-diagnosed asthma
- BDR ≥8%99 or (if BDR<8%) increased airway responsiveness to methacholine (PD20 <16.81 umol)
- Four Puerto Rican grandparents
- Steroid naïve (no treatment with ICS, nasal, or oral corticosteroids in the prior 4 weeks)
- Parental consent and child's assent to participate in the study
Key exclusion criteria (5 listed)
- Chronic disease (i.e. respiratory, liver, cardiac, renal, neurologic) other than asthma
- Severe asthma, as evidenced by: a) intubation for asthma at any time, or b) ≥3 hospitalizations or ≥6 visits to the emergency department/urgent care in the previous year, or c) chronic/continuous need for medications other than single controller therapy [ICS or leukotriene inhibitors] and short-acting β2-agonists
- Current smoking or former smoking if ≥5 pack-years
- Inability to perform acceptable spirometry
- FEV1 <60% of predicted
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inhaled corticosteroid (mometasone)Also: AsmanexThe investigators are not measuring the effect of the intervention (ICS), but rather the effect of stress (which is not being intervened on), and this is thus an observational study. The ICS is given to children with asthma in whom an ICS is clinically indicated | Drug | Study cohort (all children with asthma) |
Primary outcome
Bronchodilator response (BDR)
Time frame: 15 minutes
BDR will be measured as the change in forced expiratory volume in 1 second (FEV1) after administration of a short-acting bronchodilator (albuterol)
Response to inhaled corticosteroids (ICS)
Time frame: Six weeks
ICS response will be measured as change in forced expiratory volume in 1 second (FEV1) and as change in the xhild-Asthma Control Test (C-ACT) score, following six weeks of ICS administration
DNA methylation and gene expression differences
Time frame: Six weeks
The investigators will examine whether child stress is associated with DNA methylation or gene expression differences, and such differences will then be tested for association with BDR or ICS response (measured as above)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan C Celedon, MD, DrPH principal investigator
University of Pittsburgh
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma in Children, run by University of Pittsburgh at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bronchodilator response (BDR) (time frame: 15 minutes). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2025.