Clinical trial NCT01750411: Severe Asthma Research Program - Wake Forest University
Official title: The Severe Asthma Research Program at Wake Forest University - Longitudinal Phenomics and Genetics of Severe Asthma.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Severe Persistent Asthma
Keywords: Severe Asthma
SARP
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-12-17
Enrollment: 87
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The target recruitment goal for each center is 75% adults (age 18 and older) and 25% children age 6-17 years. Within the pediatric age group, an attempt will be made to enroll equal numbers of children 6-11 and 12-17 years of age. Similarly, an attempt will be made to enroll at least 50% females and 30% minorities.

Given the mission of SARP, a diverse sample of subjects with asthma is needed to gain better understanding of asthma and its endotypes. Because there are a number of respiratory disorders that may be confused with asthma or confound asthma assessment, SARP enrollees must meet the all following eligibility criteria as outlined below:

Brief summary: The mission of SARP is to improve the understanding of severe asthma through the integrated study of the effect of genetics on the clinical and biological features of asthma and to investigate how these change over time. The ultimate goal of these efforts is to promote better treatments for severe asthma.

Detailed description: The mission of the SARP is to improve the understanding of severe asthma to develop better treatments. The SARP will gain a better understanding of asthma and its endotypes, in children and adults, by defining the disease at the molecular and cellular levels in the context of the temporal phenotypic expression of the disease. To this end, the SARP investigators will utilize both mechanistic and evoked phenotype approaches to: 1) characterize developmental molecular, cellular and physiologic phenotypes in children and adults with mild to severe asthma, and 2) to further elucidate the evolving pathobiology and pathogenesis of severe asthma and its sub-phenotypes and 3) compare these features over time. This approach involves a shared longitudinal protocol conducted across all participating centers which includes common information on all SARP participants. Additionally, SARP investigators have each identified mechanistic research questions to be included in the shared longitudinal protocol. At Wake Forest University investigators are specifically interested in genetic influences on disease severity and the use of statistical modeling techniques to better understand disease phenotypes. Together, these longitudinal and mechanistic approaches will enable prediction of phenotype stability/fluctuation and pharmacologic responses and identification of novel, disease-modifying targets for treatment.

Eligibility criteria: Inclusion Criteria:

1. Physician diagnosis of asthma,
2. Age 6 years and older
3. Evidence of historical reversibility, including either:

   * FEV1 bronchodilator reversibility ≥ 12%, or
   * Airway hyperresponsiveness reflected by methacholine PC20≤16 mg/mL.

Exclusion Criteria:

1. No primary medical caregiver
2. Pregnancy (only if undergoing methacholine challenge or bronchoscopy)
3. Current smoking
4. 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)
5. 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 asthma symptoms, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways
6. History of premature birth before 35 weeks gestation
7. Planning to relocate from the clinical center area before study completion

Primary outcomes:
measure: Change in pulmonary function over time
timeFrame: 36 months
Secondary outcomes:
measure: Frequency of severe asthma exacerbations
timeFrame: 36 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: University of Arizona Department of Medicine
name: Eugene R Bleecker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Arizona Department of Medicine
name: Deborah A Meyers, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Wendy C Moore, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.