Study of Acid Reflux Therapy for Children With Asthma

Asthma Clinical Trial

— SARCA  

Official title:

Study of Acid Reflux Therapy for Children With Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00604851
• Other study ID #: IRB00001316
• Secondary ID: 5U01HL080433-02S
• Status: Completed
• Phase: N/A
• First received: December 27, 2007
• Last updated: January 30, 2018
• Start date: September 2006
• Est. completion date: December 2011

Study information

• Verified date: January 2018
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gastroesophageal reflux (GER) is frequent in children with asthma, can induce bronchspasm, and increase airway reactivity. Children with asthma are often treated for GER with drugs to supress gastric acid production. However, this treatment is expensive, and with unproven benefit. The primary objective of this study is to conduct a multi-site, randomized, clinical trial to test the hypothesis that treatment of GER with lansoprazole, an approved proton pump inhibitor, will decrease the frequency of exacerbations in children with poorly controlled asthma. The study will include 300 asthmatic children treated with inhaled corticosteroids, 6-16 years of age, with poor control defined by frequent symptoms, excessive beta agonist use, or frequent exacerbations. Participants will be randomly assigned to treatment with either lansoprazole or placebo for 6 months. The presence, severity, and relationship of GER to asthma symptoms will be determined with 24 hour esophageal pH monitoring, but randomization to treatment will not be influenced by the presence or severity of GER. The primary outcome measure is the proportion of participants who have exacerbations of asthma defined by diaries and interviews. Secondary outcome measures include asthma symptom and control scores, GER symptoms, lung function, and unscheduled health care contacts. Pre-defined subgroup analyses will examine the relationship between specific clinical features and the response to lansoprazole. Treatment response will also be evaluated with 3-hour post-dose plasma lansoprazole concentrations, and related to polymorphisms in the gene CYP2C19, the cytochrome P450 pathway, and interleukin-1 (IL-1) beta, a pro-inflammatory cytokine. Tertiary studies will determine how the magnitude of GER impacts airways inflammation, as measured by the concentrations of hydrogen ions (pH) and nitric oxide in expired breath. The results of this trial sould have a major impact on the understanding and treatment of GER in children with asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 306
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 16 Years

Eligibility

Inclusion Criteria:Age:

• 6-16 years

• Asthma: Physician diagnosed asthma, mathacholine PC20<16 mg/ml, treatment with a stable dose of daily inhaled corticosteroid equivalent to 200 micrograms/day of fluticasone or greater for 8 weeks or longer

• Poor asthma control: Use of beta-agonist for asthma symptoms twice/week or more, nocturnal awakening with asthma symptoms more than once per week, 2 or more emergency department, unscheduled physician visit, prednisone course, or hospitalizations for asthma in the past 12 months, Score of 1.5 or greater on the Juniper Scale of Recent Asthma Control

• Absence of GERD symptoms: No symptoms clearly attributed to GER at the time of enrollment.

Exclusion Criteria:

• Surgery: Previous anti-reflux or peptic ulcer surgery, previous tracheo-esophageal fistula repair

• Pulmonary Function:FEV1 <60% predicted normal as measured immediately before methacholine bronchoprovocation. Methacholine bronchoprovocation limited to participants with an FEV1 >70% of predicted in accordance with FDA indication

• Other major chronic illnesses: Any major chronic illness including but not limited to non-skin cancer, cystic fibrosis, bronchiectasis, myelomeningocele, sickle cell anemia, endocrine disease, congenital heart disease, congestive heart failure, stroke, severe hypertension, insulin-dependent diabetes mellitus, renal failure, liver disorders, immunodeficiency states, significant neurodevelopmental delay or behavioral disorders or other conditions that would interfere with participation in the study.

• Medication Use: Anti-reflux medication (proton pump inhibitors, H2 blockers, bethanecol, metaclopromide) within 1 month; Theophylline preparations, azoles, anti-coagulants, insulin, digitalis, any investigative drug within 2 months.

• Drug allergy: Previous adverse effects from lansoprazole, other proton pump inhibitors or methacholine challenge.

• Non-adherence: Inability or unwillingness of the legal guardian to provide consent or inability or unwillingness of the child to provide assent. Inability to swallow study medication. Inability to perform baseline measurements. Less than 80% completion of screening period diaries. Inability to contact by telephone. Intention to move out of the areqa within 6 months. No pregnancy.

Related Conditions & MeSH terms

• Asthma
• Gastroesophageal Reflux
• Heartburn

Intervention

Drug:
• lansoprazole
participants < 30 kg: 15 mg by mouth once daily; participants >= 30 kg: 30 mg by mouth once daily
• placebo
placebo medication taken by mouth once daily

Locations

Country	Name	City	State
United States	Emory Childrens Center	Atlanta	Georgia

Sponsors (12)

Lead Sponsor	Collaborator
Emory University	American Lung Association, Baylor College of Medicine, Duke University, Johns Hopkins University, National Heart, Lung, and Blood Institute (NHLBI), Nemours Children's Clinic, New York Medical College, Ohio State University, University of Manitoba, University of Vermont, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Asthma Control Questionnaire Score at the 24 Week Visit.	The Asthma Control Questionnaire contains 7 items that are scored on a 7 point scale (range is 0 to 6). The scores are then summed and divided by 7 to reveal an overall score. A lower score indicates better asthma control. The results reflect the difference in the Asthma Control Questionnaire Score between baseline (randomization visit) and 24 weeks of treatment.	Baseline and 24 weeks
Secondary	Asthma Symptom and Control Scores (Score Change in ASUI)	The Asthma Symptom Utility Index (ASUI) is a validated 2-week recall questionnaire that addresses issues of asthma control. ASUI measures the frequency and severity of asthma symptoms. This is a 10-item questionnaire. Items are weighted according to patient preferences. The summary score is a continuous scale from 0 to 1, with lower scores indicating worse asthma symptoms. Score change in ASUI from baseline are calculated.	Baseline and 24 weeks
Secondary	Percent of Patients With GER	GER symptoms were measured by esophageal pH monitoring (called a "pHprobe") in a subset of participants, so the sample size is different.The GERD symptoms were assessed only once during baseline period.	Baseline
Secondary	Lung Function (Change for FEV 1 Response From Baseline)	Lung Function was assessed by forced expiratory spirometry for FEV 1. Lung function (FEV1) was measured as a continuous variable. Change in FEV 1 from baseline was calculated.	Baseline and 24 weeks
Secondary	Episodes of Poor Asthma Control	The number of participants analyzed for poor asthma outcome differs from number of participants in the study due to missing data.	Assessed at Baseline and 24 weeks, week 24 reported