Evaluation of an Asthma Treatment Strategy Based on Exhaled Nitric Oxide Measurements in Adolescents - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00114413

Purpose

The purpose of this study 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.

Condition	Intervention
Asthma	Drug: Inhaled corticosteroids Procedure: eNO measurement

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver), Active Control, Parallel Assignment, Efficacy Study
Official Title:	Asthma Control Evaluation (ACE): A Biomarker-Based Approach to Improving Asthma Control and Mechanistic Studies (DAIT ICAC-02)

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Nitric oxide Corticosteroids

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Mean maximum symptom days per 2 weeks, as assessed by questionnaire [ Time Frame: At Visits 3 and 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Days with wheeze [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Days of slowed down or discontinued physical activities due to asthma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Nights awoken due to asthma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Days on which plans were changed due to asthma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Days missed school/work due to asthma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Unscheduled office/clinic visit due to asthma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Emergency room/urgent care center due to asthma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Hospitalization due to asthma [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Number of asthma exacerbations requiring prednisone or prednisone equivalent [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	500
Study Start Date:	August 2004
Study Completion Date:	November 2006
Primary Completion Date:	November 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Reference Strategy: Active Comparator Participants in the reference strategy group will undergo the eNO procedure but will follow NAEPP guidelines alone for asthma treatment without eNO measurements for the rest of the study.	Drug: Inhaled corticosteroids Used for both regular asthma control and as a rescue inhaler
Biomarker Strategy: Experimental Participants in the biomarker strategy group will follow NAEPP treatment guidelines, as well as eNO measurements, to determine asthma treatment at each study visit.	Drug: Inhaled corticosteroids Used for both regular asthma control and as a rescue inhaler Procedure: eNO measurement measured by Aerocrine® NIOX device

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.

This study will last 46 weeks and will comprise 8 study visits. At Visit 1, the Aerocrine® NIOX device will be used to perform eNO measurements on all participants. A physical exam will be performed and participants will be asked to complete asthma-related questionnaires. Participants will be assigned a 3-week individual asthma control regimen; the regimen will be determined by evaluations performed during screening. At the end of 3 weeks, participants will have a home visit; during this visit, participants' home environment will be observed, dust samples will be taken, and an adherence check will be performed.

At Visit 2, participants will be randomly assigned to either the reference strategy group or the biomarker strategy group for 46 weeks. Participants in the reference strategy group will undergo the eNO procedure but will follow NAEPP guidelines alone for asthma treatment without eNO measurements for the rest of the study. Participants in the biomarker strategy group will follow NAEPP treatment guidelines as well as eNO measurements to determine asthma treatment at each study visit.

At Visits 2 through 7, participants will receive an asthma medication regimen based on symptoms, albuterol use, forced expiratory volume in one second (FEV), their current level of therapy and, for participants in the biomarker strategy group, their current eNO level. The assigned regimens may be adjusted if visit assessments indicate significant changes in condition. At each study visit, rescue bronchodilator usage, medication adherence, asthma symptoms, and medication side effects will be assessed, and the volume of air that is exhaled by the lungs will be measured; blood collection will also occur. At Visit 2, a skin prick test will be performed to determine allergies; if necessary, this test will be performed at Visit 3 or 4. At Visit 8, a final treatment regimen will be prescribed for all participants, but no medication will be given at the visit.

Eligibility

Ages Eligible for Study:	12 Years to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00114413

Locations

United States, Arizona
University of Arizona (DAIT-ICAC-01/02)
Tucson, Arizona, United States, 85724
United States, Colorado
National Jewish Medical and Research Center (DAIT-ICAC-01/02)
Denver, Colorado, United States, 80206
United States, District of Columbia
Howard University
Washington DC, District of Columbia, United States, 20010
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Mount Sinai (DAIT-ICAC-01/02)
New York, New York, United States, 10032
United States, North Carolina
Rho Federal System Division, Inc- data coordinating center
Chapel Hill, North Carolina, United States, 27517
United States, Ohio
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
United States, Texas
University of Texas Southwestern (DAIT-ICAC-01/02)
Dallas, Texas, United States, 75235
United States, Wisconsin
University of Wisconsin-an administrative site
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:

William Busse, MD

University of Wisconsin, Madison

More Information

Publications:

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.

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.

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.

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.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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.

Study ID Numbers:	DAIT ICAC-01/DAIT ICAC-02
Study First Received:	June 14, 2005
Last Updated:	February 11, 2008
ClinicalTrials.gov Identifier:	NCT00114413 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Exhaled Nitric Oxide
Lung
Urban Health
Child
Adolescent

Additional relevant MeSH terms:

Respiratory System Agents
Neurotransmitter Agents
Vasodilator Agents
Antioxidants
Bronchial Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Therapeutic Uses
Free Radical Scavengers
Endothelium-Dependent Relaxing Factors

Immune System Diseases
Asthma
Anti-Asthmatic Agents
Cardiovascular Agents
Protective Agents
Pharmacologic Actions
Nitric Oxide
Autonomic Agents
Lung Diseases
Hypersensitivity, Immediate
Peripheral Nervous System Agents
Bronchodilator Agents
Respiratory Hypersensitivity

ClinicalTrials.gov processed this record on February 08, 2010