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Study of the Mechanisms of Asthma (MAST)

This study has been completed.
Genentech, Inc.
Information provided by (Responsible Party):
University of California, San Francisco Identifier:
First received: January 2, 2008
Last updated: December 5, 2013
Last verified: December 2013
The purpose of this study is to identify the causes of asthma that were not previously suspected, to better understand the effects of inhaled steroids on asthma and to identify new way to treat asthma. In order to take advantage of the most current scientific expertise, we (scientists at UCSF) plan to work together with Genentech Inc. We believe that working with Genentech will provide the best chance of developing new treatments for asthma.

Condition Intervention Phase
Asthma Drug: Pulmicort Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Determining Mechanisms of Asthma Through Detailed Analysis of Airway Secretions and Tissues

Resource links provided by NLM:

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Gene Expression in Airway Secretions and Tissues [ Time Frame: Healthy Control: Visit 2 (at 1 week); Steroid Naive Asthmatics: Visit 2 (at 1 week); Steroid Treated Asthmatics: Visit 5 (at 9 weeks) ]
    The primary outcome measure for this study is the scaled mean value of three gene expression markers of IL-13 in the airway: PERIOSTIN, calcium-activated chloride channel regulator 1 (CLCA1), and plasminogen activator inhibitor-2 (SERPINB2). First, for each of the three interleukin-13 (IL-13) signature genes, the log (base-2) transformed relative expression value for each subject is measured using real-time polymerase chair reaction (PCR) and normalized with the geometric mean of 5 housekeeping genes. Next, these values are centered (by subtracting the mean for that gene) and scaled (by dividing by the standard deviation for that gene) so that each gene makes an equal, assay-independent contribution to the Th2 phenotype. Then, for each subject, the arithmetic mean of the three centered & scaled genes is calculated, producing the "three-gene-mean" metric.

Enrollment: 127
Study Start Date: April 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: B
Asthmatics not on inhaled corticosteroids who will be put on an inhaled steroid during the study
Drug: Pulmicort
inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Other Name: Budesonide
No Intervention: A
Healthy, non-asthmatics who will not be put on any intervention
Active Comparator: C
Asthmatics, who are already on inhaled corticosteroids who will be put on standardized dose of inhaled corticosteroids
Drug: Pulmicort
inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Other Name: Budesonide

Detailed Description:
Asthma is a common airway disease with persistent unmet needs on terms of treatment. Although many asthmatics enjoy good control of their disease by using regularly scheduled corticosteroid treatment, a significant minority do not achieve optimal control with steroids and suffer asthma exacerbations which can be severe and even fatal. Asthma pathophysiology is complex and involves multiple cell types and multiple signaling mechanisms. One approach to this complexity has been to study responses of isolated airway cells to experimental conditions which model asthmatic inflammation; another has been genetic manipulations of candidate mediators of asthma in inbred mice. These studies have yielded important insights about possible mechanisms of asthma in humans, but the relevance of these mechanisms to human disease has not always been proven, and it is possible that unsuspected mechanism have not yet been revealed by these approaches. In the studies proposed here we will take an experimental approach which takes advantage of the distinct clinical phenotype of human asthma, the ability to measure steroid response in asthma, the relative ease of collecting airway cells and tissues by bronchoscopy, and the availability of new technologies such as high density microarrays which have probes for all genes in the genome or proteomics which can identify all proteins present in a biologic sample. Using this approach, we will identify differential expression of genes and proteins in airway cells and tissues in asthma that can then be explored further in cell and animal model systems to determine their potential as drug targets in asthma. We further believe that our approach will identify previously unsuspected mechanisms of action of corticosteroids in airway cells and tissues in asthma. Presently, relatively little is known about why some asthmatics respond well and some poorly to steroids and closing this gap in knowledge will help identify candidate genes and proteins to target in order to address unmet therapeutic needs in asthmatics with steroid resistant asthma.

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Group C:

  • Male and female subjects between the ages of 18 and 70 years
  • History of asthma
  • Continuous treatment with inhaled corticosteroids for at least the 6-week
  • Hyperreactivity to methacholine (provocative concentration of methacholine causing a 20% drop in forced expiratory volume in 1 second (PC20 FEV1) Methacholine ≤ 16.0 mg/mL).

Exclusion Criteria:

  • History of asthma
  • No use of oral or inhaled corticosteroids for the treatment of asthma in the past 6 weeks
  • Hyperreactivity to methacholine (PC20 FEV1 Methacholine ≤ 8.0 mg/mL).
  • At least one of the following symptoms, beta agonist use, or FEV1 criteria:

    • Asthma symptoms on at least two days per week; OR
    • Beta agonist use on at least two days per week; OR
    • Forced expiratory volume in 1 second (FEV1) < 85% predicted
  • Subjects must be non-smokers (patients who have never smoked or patients who have not smoked for 1 year and have a total pack-year smoking history < 15 packs).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00595153

United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Genentech, Inc.
Principal Investigator: John V Fahy, M.D., M.Sc. University of California, San Francisco
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of California, San Francisco Identifier: NCT00595153     History of Changes
Other Study ID Numbers: UCSF CHR# H6788-30617
Study First Received: January 2, 2008
Results First Received: September 25, 2013
Last Updated: December 5, 2013

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Hormones, Hormone Substitutes, and Hormone Antagonists processed this record on July 25, 2017