Severe Asthma Research Program - University of Virginia (SARP3)

• ClinicalTrials.gov Identifier: NCT01761058
• Recruitment Status: Unknown
• First Posted: January 4, 2013
• Last Update Posted: July 2, 2013
• Sponsor: University of Virginia
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Case Western Reserve University
• Information provided by (Responsible Party): University of Virginia

Tracking Information

• First Submitted Date: January 2, 2013
• First Posted Date: January 4, 2013
• Last Update Posted Date: July 2, 2013
• Study Start Date: December 2012
• Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 1, 2013)

Lung Function [ Time Frame: baseline and 3 years ]

decline in lung function (FEV1) over 3 years

Original Primary Outcome Measures (submitted: January 2, 2013)

Lung Function [ Time Frame: 3 years ]

decline in lung function (FEV1) over 3 years

Current Secondary Outcome Measures (submitted: July 1, 2013)

• Asthma Control Questionnaire [ Time Frame: baseline and 3 years ]
  change in score in ACQ. Subjects report having worst asthma symptoms.
• Puberty Changes [ Time Frame: baseline and 3 years ]
  Lung function will worsen in girls with severe asthma at the time of menarche and the decline will be greater in women with severe asthma than men. And fewer girls than boys will outgrow severe asthma during puberty
• Exacerbation [ Time Frame: baseline and 3 years ]
  Exacerbation requiring systemic steroids

Original Secondary Outcome Measures (submitted: January 2, 2013)

• Asthma Control Questionnaire [ Time Frame: 3 years ]
  change in score in ACQ. Subjects report having worst asthma symptoms.
• Puberty Changes [ Time Frame: 3 years ]
  Lung function will worsen in girls with severe asthma at the time of menarche and the decline will be greater in women with severe asthma than men. And fewer girls than boys will outgrow severe asthma during puberty
• Exacerbation [ Time Frame: 3 years ]
  Exacerbation requiring systemic steroids

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Severe Asthma Research Program - University of Virginia
• Official Title: The Severe Asthma Research Program at University of Virginia - Airway Redox Biochemistry as a Determinant of Asthma Phenotype During Adolescence
• Brief Summary: The overall goal of this proposal is to better understand the basis of airway remodeling in severe asthma and how remodeling changes overtime. The investigators propose to study a well characterized cohort of individuals with severe asthma using a multidisciplinary state-of-the-art-approach.
• Detailed Description: Through innovative metabolomics and redox biochemistry, methodologies that are a strength and unique to our collaborative efforts, the investigators identified clinically relevant phenotypes of asthma. The phenotypes are defined by biomarkers specific to underlying biochemical mechanistic abnormalities, including eosinophil-mediated oxidation, depletion of antioxidants and protective airway S-nitrosothiols, and airway acidification. Here,the investigators propose to study a new component that is informative for longitudinal assessment of severe asthma phenotypes: gender effects. The investigators reason that identification of the metabolic mechanism(s) underlying onset of severe asthma in young women during adolescence, and resolution of severe asthma in boys, will reveal fundamental pathophysiology of severe asthma. Importantly, we aim to develop clinical testing procedures to accurately assign metabolic asthma phenotypes; and to follow patients in each phenotype to uncover clinical longitudinal outcomes. At the conclusion of the project, we anticipate that we will have 1) developed clinically relevant tests to identify severe asthma phenotypes; 2) determined the longitudinal outcome of the phenotypes; and 3) identified the mechanisms underlying the preponderance of women in the severe asthma population. This application will focus on the development or clinically relevant metabolic tests to identify subphenotypes of adults and children with severe asthma and will lead to new targeted innovative treatments.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Blood: CBC/DIFF, total IgE, Serum, plasma, DNA, RNA, sputum, urine, exhaled breath condensate
• Sampling Method: Non-Probability Sample
• Study Population: Children with asthma (severe, well controlled)from the Charlottesville enactment area.
• Condition: Asthma
• Intervention: Not Provided

Study Groups/Cohorts

• Severe Asthma
  Subjects with Severe Asthma (SARP protocol definition)
• Well controlled asthma
  subjects with well controlled asthma

• Publications *: Dunican EM, Elicker BM, Gierada DS, Nagle SK, Schiebler ML, Newell JD, Raymond WW, Lachowicz-Scroggins ME, Di Maio S, Hoffman EA, Castro M, Fain SB, Jarjour NN, Israel E, Levy BD, Erzurum SC, Wenzel SE, Meyers DA, Bleecker ER, Phillips BR, Mauger DT, Gordon ED, Woodruff PG, Peters MC, Fahy JV; National Heart Lung and Blood Institute (NHLBI) Severe Asthma Research Program (SARP). Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018 Mar 1;128(3):997-1009. doi: 10.1172/JCI95693. Epub 2018 Feb 5.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 2, 2013): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2017
• Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Physician diagnosis of asthma

• Age 6 years to 17 years old Evidence of historical reversibility, including either;

1. FEV1 bronchodilator reversibility greater than or equal to 12%, or
2. Airway hyperresponsivesness reflected by a methacholine PC20 less than or equal to 16 mg/ml.

Exclusion Criteria:

• Exclusion criteria include any of the following:

  1. Pregnancy during the characterization phase*,
  2. Current smoking,
  3. Smoking history > 10 pack years if ≥30 years of age, or smoking history > 5 pack years if <30 years of age (Note: if a subject has a smoking history, no smoking within the past year),
  4. Other chronic pulmonary disorders associated with asthma-like symptoms, including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction (that is the sole cause of respiratory symptoms and at the PI's discretion), severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways,
  5. History of premature birth before 35 weeks gestation,
  6. Unwillingness to receive an intramuscular triamcinolone acetonide injection.
  7. Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures,
  8. Planning to relocate from the clinical center area before study completion,
  9. Any other criteria that place the subject at unnecessary risk according to the judgment of the Principal Investigator and/or attending physician(s) of record, or
  10. Currently participating in an investigational drug trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01761058
• Other Study ID Numbers: 16400; 1U10HL109164-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Virginia
• Study Sponsor: University of Virginia

Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• Case Western Reserve University

Investigators

• Principal Investigator: W. Gerald Teague, MD; University of Virginia

• PRS Account: University of Virginia
• Verification Date: July 2013