Clinical trial NCT01606826: Severe Asthma Research Program
Official title: Severe Asthma Research Program
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Asthma
Keywords: Severe
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-05-28
Enrollment: 1100
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The target study population will is 80% adults (age 18 and older) and 20% children age 6-17 years, 50% females, and 30% minorities.

Approximately 100 Healthy Control patients, matching the demographic characteristics of the asthma patients, will also be recruited in order to generate reference data for biospecimens collected from asthmatic patients.

Brief summary: The mission of the SARP is to improve the understanding of severe asthma through integrated study of its clinical and biological features and to evaluate their changes 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, the SARP investigators have each identified mechanistic research questions to be included in the shared longitudinal protocol. 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: Asthmatic Patients:

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 a methacholine PC20 ≤16 mg/mL.

Exclusion Criteria:

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 for asthma therapies.

Healthy Controls:

Inclusion criteria: Healthy subjects between the age of 18 and 65 years. Exclusion criteria

1. History of chronic diseases that affect the lungs,
2. A history suggestive of allergic rhinitis, eczema or chronic sinusitis,
3. An improvement in FEV1 of more than 12% following 4 puffs of albuterol,
4. Smoking history \> 10 pack years if ≥30 years of age, or smoking history \> 5 pack years if \<30 years of age, or any smoking within the past year,
5. Respiratory tract infection within the past 4 weeks,
6. Pregnancy,
7. History of premature birth (\<35 weeks).

Primary outcomes:
measure: Pulmonary function test results
timeFrame: 36 months after enrollment
Secondary outcomes:
measure: Frequency of severe asthma exacerbations
timeFrame: 36 months after enrollment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital, Boston
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
affiliation: University of Pittsburgh
name: Sally Wenzel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham & Women's Hospital, Boston
name: Elliot Israel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham & Women's Hospital, Boston
name: Bruce Levy, MD
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: John Fahy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Suzy Comhair, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin, Madison
name: Loren Denlinger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Wendy Moore, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kansas
name: Mario Castro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Penn State College of Medicine
name: David Mauger, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coverstone AM, Boomer JS, Lew D, Bacharier LB, Castro M; Severe Asthma Research Program (SARP) Investigators. Type 2 inflammation in the sputum of adolescents with asthma. Ann Allergy Asthma Immunol. 2021 Mar;126(3):297-299. doi: 10.1016/j.anai.2020.11.018. Epub 2020 Dec 2. No abstract available.
citation: Ross KR, Gupta R, DeBoer MD, Zein J, Phillips BR, Mauger DT, Li C, Myers RE, Phipatanakul W, Fitzpatrick AM, Ly NP, Bacharier LB, Jackson DJ, Celedon JC, Larkin A, Israel E, Levy B, Fahy JV, Castro M, Bleecker ER, Meyers D, Moore WC, Wenzel SE, Jarjour NN, Erzurum SC, Teague WG, Gaston B. Severe asthma during childhood and adolescence: A longitudinal study. J Allergy Clin Immunol. 2020 Jan;145(1):140-146.e9. doi: 10.1016/j.jaci.2019.09.030. Epub 2019 Oct 14.
citation: Fitzpatrick AM, Szefler SJ, Mauger DT, Phillips BR, Denlinger LC, Moore WC, Sorkness RL, Wenzel SE, Gergen PJ, Bleecker ER, Castro M, Erzurum SC, Fahy JV, Gaston BM, Israel E, Levy BD, Meyers DA, Teague WG, Bacharier LB, Ly NP, Phipatanakul W, Ross KR, Zein J, Jarjour NN. Development and initial validation of the Asthma Severity Scoring System (ASSESS). J Allergy Clin Immunol. 2020 Jan;145(1):127-139. doi: 10.1016/j.jaci.2019.09.018. Epub 2019 Oct 8.
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.
citation: Ricklefs I, Barkas I, Duvall MG, Cernadas M, Grossman NL, Israel E, Bleecker ER, Castro M, Erzurum SC, Fahy JV, Gaston BM, Denlinger LC, Mauger DT, Wenzel SE, Comhair SA, Coverstone AM, Fajt ML, Hastie AT, Johansson MW, Peters MC, Phillips BR, Levy BD; National Heart Lung and Blood Institute's Severe Asthma Research Program-3 Investigators. ALX receptor ligands define a biochemical endotype for severe asthma. JCI Insight. 2017 Jul 20;2(14):e93534. doi: 10.1172/jci.insight.93534. eCollection 2017 Jul 20.
citation: Phipatanakul W, Mauger DT, Sorkness RL, Gaffin JM, Holguin F, Woodruff PG, Ly NP, Bacharier LB, Bhakta NR, Moore WC, Bleecker ER, Hastie AT, Meyers DA, Castro M, Fahy JV, Fitzpatrick AM, Gaston BM, Jarjour NN, Levy BD, Peters SP, Teague WG, Fajt M, Wenzel SE, Erzurum SC, Israel E; Severe Asthma Research Program. Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma. Am J Respir Crit Care Med. 2017 Jun 1;195(11):1439-1448. doi: 10.1164/rccm.201607-1453OC.