Implications and Stability of Clinical and Molecular Phenotypes of Severe Asthma

NCT01748175 | Completed DMC

• 1 other identifier: 1010HL109152-01
• Study Type: observational
• Target: 715
• Locations: 1 country
• Sites: 1

Brief Summary

The Severe Asthma Research Program III is an NIH cooperative agreement involving 7 clinical centers that encompass a multidisciplinary partnerships between asthma clinician-scientists and scientists with expertise in immunology, pulmonary physiology, molecular genetics, molecular phenotyping, imaging, and bioinformatics. These clinical centers will jointly recruit volunteers with asthma for an observational longitudinal follow-up study. However, centers will also conduct specific mechanistic research projects at each participating institution. The University of Pittsburgh's SARP III study will determine the molecular and clinical stability of asthma phenotypes over time.

Conditions

Asthma; Severe Persistent Asthma

Keywords

Severe asthma; longitudinal study; phenotypes

Outcome Measures

Primary Outcomes (2)

• Airway lumen mast cells

  Determine the impact of mast cell markers on human airway epithelial cell phenotype and function.

  Once, during bronchoscopy

• Longitudinal asthma phenotype

  Determine the long term stability and implications of previously identified clinical and molecular asthma phenotypes, specifically the mast cell signature, and identify potential systemic biomarkers for these phenotypes. Determine whether a biomarker for the lung mast cell signature can be identified in serum/plasma of both adult and pediatric severe asthmatics

  Change rates, determined annually for three years

Study Arms (1)

Longitudinal follow up

Patients will undergo a characterization phase, which includes a baseline evaluation (1 visit), and a steroid responsiveness evaluation (2 visits). The longitudinal phase will include 3 office visits (annually) over 36 months with bi-annual phone calls. During the study patients will answer questionnaires, perform lung function testing and provide blood, urine, sputum and exhaled breath condensate samples.

Drug: Triamcinolone Acetonide

Interventions

Triamcinolone Acetonide DRUG

Each subject that meets inclusion/exclusion criteria will receive triamcinolone acetonide intramuscularly at the end of visit 2. Adults ≥18 years will receive 40 mg triamcinolone acetonide. Children 6-17 years will receive 1 mg/kg triamcinolone acetonide (up to 40 mg maximum). Triamcinolone acetonide will be administered as a single intramuscular dose deep in the gluteal region

Also known as: Kenalog

Longitudinal follow up

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with asthma meeting inclusion and exclusion criteria will be recruited from 7 SARP III participating clinical centers. The clinical centers are located at Brigham and Women's Hospital (with co-investigators at Children's Hospital), the University of California San Francisco, the University of Pittsburgh, the University of Virginia (with co-investigators at the Cleveland Clinic, Case Western Reserve and Virginia Commonwealth University), the University of Wisconsin, Wake Forest School of Medicine (with co-investigators at Emory University), and Washington University in St. Louis (with co-investigators at the University of Iowa).

You may qualify if:

• Previous asthma diagnosis
• FEV1 bronchodilator reversibility ≥12% or airway hyperresponsiveness reflected by a methacholine PC20 ≤16 mg/mL (Historical methacholine data from previous NIH trial \[SARP I or II, AsthmaNet, ALA-ACRC, ACRN or CARE\] will be allowed).

You may not qualify if:

• Pregnancy during the characterization phase
• Current smoking,
• 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),
• 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,
• History of premature birth before 35 weeks gestation,
• Unwillingness to receive an intramuscular triamcinolone acetonide injection.
• Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures,
• Planning to relocate from the clinical center area before study completion,
• 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
• Currently participating in an investigational drug trial.
• Healthy Controls:
• Healthy subjects between the age of 18 and 65
• At least 3 of the 7 subjects per center should be aged 35 or older
• History of chronic diseases that affect the lungs: Chronic airway disease (asthma, cystic fibrosis, COPD, chronic bronchitis, bronchiectasis); Interstitial lung disease, sarcoidosis, occupational lung disease; Obstructive sleep apnea; Vocal cord dysfunction; Severe scoliosis or chest wall deformities.
• A history suggestive of allergic rhinitis (based on the best judgment of the physician investigator).

Sponsors & Collaborators

• Sally E. Wenzel MD: lead

Study Sites (1)

Asthma Institute, UNiversity of Pittsburgh and University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• DeBoer MD, Phillips BR, Mauger DT, Zein J, Erzurum SC, Fitzpatrick AM, Gaston BM, Myers R, Ross KR, Chmiel J, Lee MJ, Fahy JV, Peters M, Ly NP, Wenzel SE, Fajt ML, Holguin F, Moore WC, Peters SP, Meyers D, Bleecker ER, Castro M, Coverstone AM, Bacharier LB, Jarjour NN, Sorkness RL, Ramratnam S, Irani AM, Israel E, Levy B, Phipatanakul W, Gaffin JM, Gerald Teague W. Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma. BMC Pulm Med. 2018 Apr 10;18(1):58. doi: 10.1186/s12890-018-0612-x.

  PMID: 29631584 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA samples

MeSH Terms

Conditions

Asthma

Interventions

Triamcinolone Acetonide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Sally E Wenzel, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 27, 2012
• First Posted: December 12, 2012
• Study Start: January 1, 2013
• Primary Completion: December 1, 2021
• Study Completion: January 1, 2022
• Last Updated: September 16, 2022

Record last verified: 2022-09

Locations

US (1)