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

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ClinicalTrials.gov Identifier: NCT03134755
Recruitment Status : Not yet recruiting
First Posted : May 1, 2017
Last Update Posted : November 8, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

April 26, 2017
May 1, 2017
November 8, 2017
January 2018
December 31, 2020   (Final data collection date for primary outcome measure)
  • 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)
  • 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 ]
    We 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)
Complete list of historical versions of study NCT03134755 on ClinicalTrials.gov Archive Site
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Stress and Treatment Response in Puerto Rican Children With Asthma
Stress and Treatment Response in Puerto Rican Children With Asthma
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.
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).
Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:
Nasal epithelial samples for DNA and RNA extraction
Non-Probability Sample
300 Puerto Rican children with mild to moderate persistent asthma, ages 9 to 14 years. Of these children, 200 will be recruited from the Puerto Rico Group Insurance Plan and 100 will be recruited from clinical practices in Pediatric Pulmonary Medicine or Pediatric Allergy.
Asthma in Children
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
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)
Intervention: Drug: Inhaled corticosteroid (mometasone)
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
300
June 30, 2021
December 31, 2020   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
9 Years to 14 Years   (Child)
No
Contact: Glorisa Canino, PhD 787 754-8624 glorisa.canino@upr.edu
Contact: Edna Acosta-Perez, PhD 787 754-8624 edna.acosta2@upr.edu
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NCT03134755
PRO17030493
R01HL117191 ( U.S. NIH Grant/Contract )
No
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Juan Celedon, MD, University of Pittsburgh
University of Pittsburgh
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Juan C Celedon, MD, DrPH University of Pittsburgh
University of Pittsburgh
November 2017