Clinical trial NCT00114413: Evaluation of an Asthma Treatment Strategy Based on Exhaled Nitric Oxide Measurements in Adolescents
Official title: Asthma Control Evaluation (ACE): A Biomarker-Based Approach to Improving Asthma Control and Mechanistic Studies (DAIT ICAC-02)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: Exhaled Nitric Oxide
Lung
Urban Health
Child
Adolescent
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2005-06-15
Enrollment: 547
Sex: ALL
Minimum age (years): 12
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of ICAC-01 is to determine whether an asthma treatment strategy that measures exhaled nitric oxide (eNO) to indicate disease progression is more effective in treating asthma symptoms when combined with existing asthma treatment guidelines than treatment using the guidelines alone.

Detailed description: Over the past two decades, the prevalence of asthma has dramatically increased in many parts of the world. The current National Asthma Education and Prevention Program (NAEPP) identifies inhaled corticosteroids (ICS) as the preferred long-term control therapy for all forms of persistent asthma. However, there is still a significant proportion of patients with persistent asthma who are not receiving ICS therapy or do not follow their treatment plan. Individualized asthma treatment plans are needed. The use of biomarkers, in addition to NAEPP guidelines, may help enhance the level of asthma assessment, guide medication regimens, and improve overall asthma control. This study will determine whether NAEPP-recommended treatment, combined with eNO measurement, is more effective in reducing asthma symptoms than NAEPP-recommended treatment alone. ICAC-01 will last 46 weeks and will comprise 8 study visits.

ICAC-01 also includes a mechanistic sub-study (ICAC-02). Its primary objective is to determine whether "highly sensitized", compared to "weakly sensitized" asthmatic subjects have more severe asthma, as defined by the levels at randomization to the completion of ICAC-01. To address the primary objective of ICAC-02, the study will include all the participants enrolled in ICAC-01 with dust mite-, cockroach- and/or alternaria-specific IgE levels within certain parameters.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of asthma made by a doctor over a year prior to study entry OR symptoms have been present more than a year if the diagnosis was made less than a year prior to study entry
* Have symptoms consistent with persistent asthma OR have evidence of uncontrolled disease. More information on this criterion can be found in the DAIT ICAC-01 protocol.
* Currently reside in a pre-selected area containing at least 20% of households below the U.S. government poverty level
* Do not smoke and have not used smokeless tobacco products in the year prior to study entry
* Able to perform eNO measurement procedures and spirometry at study screening
* Parent or guardian willing to provide informed consent, if applicable
* History of clinical varicella (chicken pox) or have received varicella vaccine
* Planning to stay in the area for the next 12 months
* Primary language is English. Spanish speakers may enroll at centers with Spanish-speaking staff.
* Parent or guardian primarily speaks English (or Spanish at centers with Spanish-speaking staff), for participants with parent or guardian providing informed consent
* Willing to allow the study physician to manage disease for the duration of the study
* Willing to change asthma medications in order to follow the protocol

Exclusion Criteria:

* Adherence to controller medication between Visits 1 and 2 is less than 25%. More information on this criterion can be found in the DAIT ICAC-01 protocol.
* Determined to have mild intermittent asthma at Visit 1
* Have had a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure in the 5 years prior to study entry
* Have significant medical illnesses other than asthma. More information on this criterion can be found in the DAIT ICAC-01 protocol.
* Unable to use a metered-dose inhaler for administration of a beta-agonist rescue medication or a dry powder inhaler for the administration of asthma controller regimens
* Known hypersensitivity to any medications commonly used for the treatment of asthma
* Have not completed a home evaluation within 4 weeks of study screening
* Currently participating in another asthma-related drug or intervention study, or have participated in another asthma-related drug or intervention study in the month prior to study entry
* Does not sleep at least 4 nights per week in one home
* Lives with a foster parent (not applicable if patient is able to provide informed consent)
* Does not have access to a phone
* Requires certain medications. More information on this criterion can be found in the DAIT ICAC-01 protocol.
* Urine cotinine level above 100 ng/ml at study screening
* Pregnant or breastfeeding

Primary outcomes:
measure: Mean maximum symptom days per 2 weeks, as assessed by questionnaire
timeFrame: At Visits 3 and 8
Secondary outcomes:
measure: Days with wheeze
timeFrame: Throughout study
measure: Days of slowed down or discontinued physical activities due to asthma
timeFrame: Throughout study
measure: Nights awoken due to asthma
timeFrame: Throughout study
measure: Days on which plans were changed due to asthma
timeFrame: Throughout study
measure: Days missed school/work due to asthma
timeFrame: Throughout study
measure: Unscheduled office/clinic visit due to asthma
timeFrame: Throughout study
measure: Emergency room/urgent care center due to asthma
timeFrame: Throughout study
measure: Hospitalization due to asthma
timeFrame: Throughout study
measure: Number of asthma exacerbations requiring prednisone or prednisone equivalent
timeFrame: Throughout study
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona (DAIT-ICAC-01/02)
state: Arizona
city: Denver
country: United States
facility: National Jewish Medical and Research Center (DAIT-ICAC-01/02)
state: Colorado
city: Washington DC
country: United States
facility: Howard University
state: District of Columbia
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mount Sinai (DAIT-ICAC-01/02)
state: New York
city: Chapel Hill
country: United States
facility: Rho Federal System Division, Inc- data coordinating center
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern (DAIT-ICAC-01/02)
state: Texas
city: Madison
country: United States
facility: University of Wisconsin-an administrative site
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: William Busse, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reid DW, Johns DP, Feltis B, Ward C, Walters EH. Exhaled nitric oxide continues to reflect airway hyperresponsiveness and disease activity in inhaled corticosteroid-treated adult asthmatic patients. Respirology. 2003 Dec;8(4):479-86. doi: 10.1046/j.1440-1843.2003.00495.x.
citation: Strunk RC, Szefler SJ, Phillips BR, Zeiger RS, Chinchilli VM, Larsen G, Hodgdon K, Morgan W, Sorkness CA, Lemanske RF Jr; Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute. Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol. 2003 Nov;112(5):883-92. doi: 10.1016/j.jaci.2003.08.014.
citation: Langley SJ, Goldthorpe S, Custovic A, Woodcock A. Relationship among pulmonary function, bronchial reactivity, and exhaled nitric oxide in a large group of asthmatic patients. Ann Allergy Asthma Immunol. 2003 Oct;91(4):398-404. doi: 10.1016/S1081-1206(10)61688-2.
citation: Jones SL, Herbison P, Cowan JO, Flannery EM, Hancox RJ, McLachlan CR, Taylor DR. Exhaled NO and assessment of anti-inflammatory effects of inhaled steroid: dose-response relationship. Eur Respir J. 2002 Sep;20(3):601-8. doi: 10.1183/09031936.02.00285302.
citation: Szefler SJ, Mitchell H, Sorkness CA, Gergen PJ, O'Connor GT, Morgan WJ, Kattan M, Pongracic JA, Teach SJ, Bloomberg GR, Eggleston PA, Gruchalla RS, Kercsmar CM, Liu AH, Wildfire JJ, Curry MD, Busse WW. Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial. Lancet. 2008 Sep 20;372(9643):1065-72. doi: 10.1016/S0140-6736(08)61448-8.
citation: Arroyave WD, Rabito FA, Carlson JC, Sever ML, Lefante J. Asthma severity, not asthma control, is worse in atopic compared with nonatopic adolescents with asthma. Ann Allergy Asthma Immunol. 2016 Jan;116(1):18-25. doi: 10.1016/j.anai.2015.10.015. Epub 2015 Nov 7.