AsthmaPhase 1MASTNCT00595153
Study of the Mechanisms of Asthma
A Phase 1 study testing Pulmicort in people with Asthma, run by University of California, San Francisco at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- Pulmicort
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Jun 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Determining Mechanisms of Asthma Through Detailed Analysis of Airway Secretions and Tissues
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- Pulmicort
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PulmicortDrug
Also called Budesonide
inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
| Study group | Role | What they receive |
|---|---|---|
| B | Active comparator | Asthmatics not on inhaled corticosteroids who will be put on an inhaled steroid during the study Receives: Drug: Pulmicort |
| A | No intervention | Healthy, non-asthmatics who will not be put on any intervention |
| C | Active comparator | Asthmatics, who are already on inhaled corticosteroids who will be put on standardized dose of inhaled corticosteroids Receives: Drug: Pulmicort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gene Expression in Airway Secretions and Tissues
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.
Measured: Healthy Control: Visit 2 (at 1 week); Steroid Naive Asthmatics: Visit 2 (at 1 week); Steroid Treated Asthmatics: Visit 5 (at 9 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2008 (estimated)
- Study startApr 2007
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- John V Fahy, M.D., M.Sc., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00595153
- Sponsor's protocol ID
- UCSF CHR# H6788-30617
- Acronym
- MAST
- Status last verified
- Dec 2013
- First submitted
- 2 Jan 2008
- Last updated
- 20 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Solberg OD, Ostrin EJ, Love MI, Peng JC, Bhakta NR, Hou L, Nguyen C, Solon M, Nguyen C, Barczak AJ, Zlock LT, Blagev DP, Finkbeiner WE, Ansel KM, Arron JR, Erle DJ, Woodruff PG. Airway epithelial miRNA expression is altered in asthma. Am J Respir Crit Care Med. 2012 Nov 15;186(10):965-74. doi: 10.1164/rccm.201201-0027OC. Epub 2012 Sep 6.
PubMed 22955319
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determining Mechanisms of Asthma Through Detailed Analysis of Airway Secretions and Tissues
- ClinicalTrials.gov ID
- NCT00595153
- Acronym / sponsor ID
- MAST / UCSF CHR# H6788-30617
- Conditions
- Asthma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Apr 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 16 Jan 2008 (estimated)
- Results
- Posted 20 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| B | Active comparator | Drug: PulmicortAsthmatics not on inhaled corticosteroids who will be put on an inhaled steroid during the study |
| A | No intervention | –Healthy, non-asthmatics who will not be put on any intervention |
| C | Active comparator | Drug: PulmicortAsthmatics, who are already on inhaled corticosteroids who will be put on standardized dose of inhaled corticosteroids |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (8 listed)
- 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:
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PulmicortAlso: Budesonideinhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks | Drug | B, C |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22955319Solberg OD, Ostrin EJ, Love MI, Peng JC, Bhakta NR, Hou L, Nguyen C, Solon M, Nguyen C, Barczak AJ, Zlock LT, Blagev DP, Finkbeiner WE, Ansel KM, Arron JR, Erle DJ, Woodruff PG. Airway epithelial miRNA expression is altered in asthma. Am J Respir Crit Care Med. 2012 Nov 15;186(10):965-74. doi: 10.1164/rccm.201201-0027OC. Epub 2012 Sep 6.
- Airway Clinical Research Center websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John V Fahy, M.D., M.Sc. principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pulmicort in people with Asthma, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00595153, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2014.