Asthma Inflammation Research

Обзор

The overall goal of the Asthma Inflammation Research \[AIR\] Translational Program is to create an integrated multidisciplinary team for the focused purpose of development of diagnostic and prognostic tests informative for airway inflammation, and for the design of innovative, targeted biologic therapeutics. The overarching aims of the AIR program are to conceptualize, develop, and test the next-generation therapeutics, and novel asthma diagnostic and prognostic tools that will allow us to improve the standard of asthma care.

Подробное описание

More than 20 million Americans suffer from asthma, and nearly half of asthma sufferers do not have their asthma under control. Although commonly diagnosed using physiological measures of airflow and bronchial hyperreactivity, asthma pathophysiology is related to chronic inflammation of the airway.

Current diagnostic evaluation and monitoring are inadequate for proposed practice guidelines. The most commonly used test for evaluation of asthma is the measurement of airflow obstruction by spirometry. The National Asthma Education Prevention Program (NAEPP) and Expert Panel Reports set forth grading of asthma severity based on the frequency of symptoms, airflow, and the need for inhaled beta-agonists. Practice guidelines outline that the goals of therapy for asthma are to: maintain normal activity with near normal parameters of lung function, prevent exacerbations that lead to tissue injury, and avoid medication toxicity. In order to facilitate these goals, NAEPP defines key components for management including disease monitoring and stepped care pharmacotherapy. Unfortunately, there is no optimal plan for monitoring inflammation, which causes us to fail in key components in management of asthma. Limited options for anti-inflammatory treatments to control asthma likewise often lead to substantial morbidities due to treatment with high doses of corticosteroids. Our AIR program plans to develop novel asthma monitoring tests and design targeted therapeutics, which altogether may reduce toxicities and improve the long-term health of patients.

Impact on broad scientific advancement. Our cumulative studies provide fundamental information on the molecular mechanisms that contribute to unresolving and excessive inflammation that leads to tissue remodeling. This mechanistic knowledge is of broad scientific importance as nearly all chronic human diseases are defined by prolonged and active inflammation, with tissue destruction, and failed attempts at healing. Thus, our investigations will provide comprehensive knowledge and consequent translational deliverables that may be widely applicable as diagnostic strategies and therapies in other chronic inflammatory diseases.

Вмешательства

• Пищевая добавка Nutritional approach for asthma
  participants will be provided a medium chain triglyceride supplement or placebo
• Пищевая добавка Low Caloric Shake
  participants will be provided a low caloric dietary shake
• Биопрепарат whole lung allergen challenge
  inhalation of allergens by allergic patients with or without asthma, will be used to define mechanisms underlying the development of airway inflammation

Первичные конечные точки

• Maintaining a tolerance to Medium Chain Triglyceride (MCT) additive for Asthmatics [Срок оценки: 24 weeks]

Вторичные конечные точки (4)

• Improvement of lung function by spirometry testing [Срок оценки: 24 weeks]
• Asthma Quality of Life Questionnaire [Срок оценки: 24 weeks]
• Asthma Control Test [Срок оценки: 24 weeks]
• Gastrointestinal tolerance of a Medium Chain Triglyceride additive to a normal diet in Asthmatics [Срок оценки: 12]

Критерии участия

Критерии включения

• Asthma diagnosed by a medical specialist and/or history of positive methacholine rest and/or reversibility of >10% of FEV1
• FEV1 is within acceptable limits
• Informed Consent is present

Критерии исключения

• Diabetes (fasting blood sugar >110 mg/dL)
• Any milk allergies
• Coconut allergies
• BMI >40 kg/m2,
• Inability to maintain diet intervention
• Current smoking or smoking history of greater than 10 pack-years
• Any other significant respiratory or cardiac disease or the presence of clinically important comorbidities, including, uncontrolled coronary artery disease, acute or and chronic renal failure

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Одна группа

Маскирование

Четверное слепое

Основная цель

Другое

Центры проведения

США · 1 центр

• Cleveland Clinic — Cleveland

Публикации

• National Asthma Education and Prevention Program. National Asthma Education and Prevention Program. Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics--2002. J Allergy Clin Immunol. 2002 Nov;110(5 Suppl):S141-219. No abstract available. PMID 12542074
• National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007 Nov;120(5 Suppl):S94-138. doi: 10.1016/j.jaci.2007.09.043. PMID 17983880
• Dweik RA, Sorkness RL, Wenzel S, Hammel J, Curran-Everett D, Comhair SA, Bleecker E, Busse W, Calhoun WJ, Castro M, Chung KF, Israel E, Jarjour N, Moore W, Peters S, Teague G, Gaston B, Erzurum SC; National Heart, Lung, and Blood Institute Severe Asthma Research Program. Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype among patients with asthma. Am J Respir Crit C PMID 20133930
• Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981 Jun;123(6):659-64. doi: 10.1164/arrd.1981.123.6.659. PMID 7271065
• Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995 Sep;152(3):1107-36. doi: 10.1164/ajrccm.152.3.7663792. No abstract available. PMID 7663792
• Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108. PMID 9872837
• Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax. 1992 Feb;47(2):76-83. doi: 10.1136/thx.47.2.76. PMID 1549827
• Dweik RA, Comhair SA, Gaston B, Thunnissen FB, Farver C, Thomassen MJ, Kavuru M, Hammel J, Abu-Soud HM, Erzurum SC. NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2622-7. doi: 10.1073/pnas.051629498. Epub 2001 Feb 20. PMID 11226289

Идентификаторы

NCT: NCT01536522 · 10-1049 · PAR-09-185

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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