Stress and Treatment Response in Puerto Rican Children With Asthma (STAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03134755
Recruitment Status : Recruiting
First Posted : May 1, 2017
Last Update Posted : December 11, 2018
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Juan Celedon, MD, University of Pittsburgh

Brief 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.

Condition or disease Intervention/treatment
Asthma in Children Drug: Inhaled corticosteroid (mometasone)

Detailed Description:
Puerto Rican (PR) children share a disproportionate burden from asthma in the U.S. The investigators have demonstrated that in PR children, a variety of psychological stressors -including physical or sexual abuse, exposure to violence, and parental psychopathology- 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 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 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 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 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 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 children).

Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Stress and Treatment Response in Puerto Rican Children With Asthma
Actual Study Start Date : May 15, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Steroids
Drug Information available for: Mometasone

Group/Cohort Intervention/treatment
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)
Drug: Inhaled corticosteroid (mometasone)
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
Other Name: Asmanex

Primary Outcome Measures :
  1. 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)

  2. 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

  3. 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)

Biospecimen Retention:   Samples With DNA
Nasal epithelial samples for DNA and RNA extraction

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   9 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
300 Puerto Rican children with mild to moderate persistent asthma, ages 9 to 17 years. Of these children, 200 will be recruited from the Puerto Rico Group Insurance Plan, non-private pediatric practices in the metropolitan area of San Juan and Caguas (Puerto Rico), and from participants in previous studies that have given their permission to be re-contacted for research studies such as this one; and 100 will be recruited from clinical practices in Pediatric Pulmonary Medicine or Pediatric Allergy.

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03134755

Contact: Glorisa Canino, PhD 787 754-8624
Contact: Edna Acosta-Perez, PhD 787 754-8624

Puerto Rico
Behavioral Sciences Research Institute, University of Puerto Rico Recruiting
San Juan, Puerto Rico, 00936
Contact: Glorisa Canino, PhD    787 754-8624   
Contact: Edna Acosta-Perez, PhD    787 672-0670   
Sponsors and Collaborators
University of Pittsburgh
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Juan C Celedon, MD, DrPH University of Pittsburgh

Responsible Party: Juan Celedon, MD, Professor, University of Pittsburgh Identifier: NCT03134755     History of Changes
Other Study ID Numbers: PRO17030493
R01HL117191 ( U.S. NIH Grant/Contract )
First Posted: May 1, 2017    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Juan Celedon, MD, University of Pittsburgh:
Puerto Rican
Health disparities
Treatment response

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Mometasone Furoate
Anti-Inflammatory Agents
Dermatologic Agents
Anti-Allergic Agents