Evaluation of an Asthma Treatment Strategy Based on Exhaled Nitric Oxide Measurements in Adolescents

NCT ID: NCT00114413

Last Updated: 2017-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 547 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2006-11-30

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Reference Strategy

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.

Group Type: ACTIVE_COMPARATOR

Inhaled corticosteroids

Intervention Type: DRUG

Used for both regular asthma control and as a rescue inhaler

Biomarker Strategy

Participants in the biomarker strategy group will follow NAEPP treatment guidelines, as well as eNO measurements, to determine asthma treatment at each study visit.

Group Type: EXPERIMENTAL

Inhaled corticosteroids

Intervention Type: DRUG

Used for both regular asthma control and as a rescue inhaler

eNO measurement

Intervention Type: PROCEDURE

measured by Aerocrine® NIOX device

Interventions

Inhaled corticosteroids

Used for both regular asthma control and as a rescue inhaler

Intervention Type: DRUG

eNO measurement

measured by Aerocrine® NIOX device

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Busse, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Arizona (DAIT-ICAC-01/02)

Tucson, Arizona, United States

National Jewish Medical and Research Center (DAIT-ICAC-01/02)

Denver, Colorado, United States

Howard University

Washington D.C., District of Columbia, United States

Children's Memorial Hospital

Chicago, Illinois, United States

Johns Hopkins University

Baltimore, Maryland, United States

Boston University School of Medicine

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mount Sinai (DAIT-ICAC-01/02)

New York, New York, United States

Rho Federal System Division, Inc- data coordinating center

Chapel Hill, North Carolina, United States

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

University of Texas Southwestern (DAIT-ICAC-01/02)

Dallas, Texas, United States

University of Wisconsin-an administrative site

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 14629652 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14610474 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14582820 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12358335 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18805335 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26560898 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID) website

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT) website

Other Identifiers

DAIT ICAC-01/DAIT ICAC-02

Identifier Type: -

Identifier Source: org_study_id