Atopic AsthmaPhase 1NCT00644514
Genetics of Asthma - Bronchoscopy Studies
A Phase 1 study testing Endotoxin - lipopolysaccharide (LPS) in people with Atopic Asthma and Healthy, run by John Sundy at 1 site in United States.
Trial summary
The purpose of this study is to identify the mediators and genes in airway epithelial and BAL cells that are differentially regulated following inhalation of endotoxin lipopolysaccharide (LPS) among study participants with allergic asthma and normal phenotypes. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Atopic Asthma, Healthy
- What is being tested?
- Endotoxin - lipopolysaccharide (LPS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Apr 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Allergic asthmatic, allergic non-asthmatic, or nonallergic nonasthmatic
- Willing/able to give informed consent \& adhere to visit/protocol schedules.
- Screening visit laboratory, C-Xray, EKG, results within normal limits
- Women of childbearing potential must have a negative serum pregnancy test
- Screening Pulmonary function testing above study criteria parameters
Who cannot join
- Systemic corticosteroid administration for asthma within the previous 90days
- Antibiotic administration within the previous 30 days.
- Viral respiratory infection within the previous 14 days.
- History of severe asthma requiring intubation.
- Occupational exposure to hay or grain dust.
- Significant exposure history to cigarette smoke
Show all 16Show fewer
- Past or present history of allergen immunotherapy to within the last 10 yrs
- Underlying illnesses that may result in altered lung function
- Students or employees under direct supervision by protocol investigators are ineligible
- Subjects allergic to medications used (or potentially used) in the study will be excluded.
- Subjects using aspirin will be excluded
- Subjects who abuse alcohol or illicit substances will be excluded
- Medication use other than for asthma, allergies or contraception
- Other medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements
- Nursing mothers
- Other investigational medication within the last 30 days
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: The Genetics of Environmental Asthma: LPS Inhalation and Bronchoscopy in Normal Subjects and Subjects With Mild Atopic Asthma
The purpose of this study is to identify the mediators and genes in airway epithelial and BAL cells that are differentially regulated following inhalation of endotoxin lipopolysaccharide (LPS) among study participants with allergic asthma and normal phenotypes. This approach is designed to identify novel genes associated with both asthma pathogenesis and asthma susceptibility. LPS, or endotoxin, a cell wall component of gram-negative bacteria, is ubiquitous in the environment, and is thought to influence both susceptibility and severity of asthma.
240 subjects (healthy adult men and women (age >18-40) with and without atopy and asthma) will complete the screening evaluations in order to establish 3 study groups of 60 subjects each. Each qualified subject will undergo an inhaled LPS endotoxin challenge followed by bronchoscopy after 24 hours, which will consist of a bronchoalveolar lavage (BAL) and endobronchial brush biopsies. BAL involves squirting a small amount of sterile salt water into one of the airways then gently taking it back out through the bronchoscope. The brush sample involves gently moving a small brush back and forth in an airway to collect cell samples. Samples of whole blood will also be obtained at various time points. RNA will be isolated from these cell populations in order to assess differential gene expression expression using microarrays.
Read the detailed description
Background:
Endotoxin or lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, is ubiquitous in the environment, and is often present in high concentrations in organic dusts, as well as in air pollution, and household dusts. There is convincing evidence that endotoxin exacerbates airflow obstruction and airway inflammation in allergic asthmatics. Additional findings indicate that allergic airways can enhance the response to inhaled endotoxin, and that endotoxin can enhance the airway response to allergens. However, when considering the interaction between endotoxin and allergens, the timing of the exposure appears to be critical. Emerging evidence suggests that early exposure to endotoxin, a potent inducer of Th1 type cytokines (IFN-g and IL-12), may minimize the risk of allergen sensitization which could has profound effects on reducing the risk of developing asthma in children. Independent of its effect in allergic asthma, several studies demonstrate that inhalation of air contaminated with endotoxin is associated with the classical features of asthma (reversible airflow obstruction and airway inflammation, and persistent airway hyperreactivity and airway remodeling). Epidemiological studies have shown that the concentration of inhaled endotoxin in the bioaerosol is strongly and consistently associated with reversible airflow obstruction among cotton workers, agricultural workers, and fiberglass workers. Importantly, the concentration of endotoxin in the bioaerosol is the most important occupational exposure associated with the development and progression of airway disease in agricultural workers. Experimentally, inhalation of endotoxin can cause reversible airflow obstruction and airway inflammation in previously unexposed healthy study subjects. The ability of the host to respond to endotoxin is highly variable, and is influenced in part by genetic factors.:
The rationale for this investigation is based on the following points:
- asthma is caused in large part by both genetic susceptibility and environmental exposure,
- a variety of immune and non-immune mechanisms can function independently or interactively to cause airway hyper-reactivity, airflow obstruction, airway inflammation, and airway remodeling,
- environmental challenges can be used to "narrow the asthma phenotype" and allow one to investigate unique gene-environment interactions that are involved in the development of biologically specific forms of asthma,
- genes that are over or under stimulated in the airway epithelia of asthmatics following inhalation challenge are important in the pathogenesis of asthma
- Conditions
- Atopic Asthma, Healthy
- Being tested
- Endotoxin - lipopolysaccharide (LPS)
- Keywords
- LPS endotoxin, Asthma
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endotoxin - lipopolysaccharide (LPS)Biological
Also called Lipopolysaccharide (LPS), NIH Clinical Center Reference Endotoxin
Nebulized 5000EU, 10,000EU, 20,000EU endotoxin doses delivered to completion. Nebulized dose inhaled 30 minutes apart if no adverse events occur after the previous dose. Fiberoptic Bronchoscopy with Bronchoalveolar Lavage (BAL) and brush samples performed 24 hours after LPS nebulization.
| Study group | Role | What they receive |
|---|---|---|
| LPS endotoxin inh f/u bronchoscopy | Experimental | Participants receive inhalation of LPS endotoxin, followed by bronchoscopy in this study. Receives: Biological: Endotoxin - lipopolysaccharide (LPS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify Genes in airway epithelial and Bronchoalveolar Lavage (BAL)that are differentially regulated following inhalation of LPS endotoxin.
Measured: bronchoscopy performed 24 hours after inhalation of endotoxin
Secondary outcomes (1)
Identify mediators in airway epithelial and BAL cells that are differentially regulated following LPS inhalation.
Measured: Bronchoscopy performed 24 hours post inhalation of endotoxin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2008 (estimated)
- Study startSep 2007
- Primary completionApr 2008
- Study completionApr 2008
Why it stopped: grant funding no longer available
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atopic AsthmaStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- John Sundy
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, John Sundy, Duke University
- Investigators
- John S Sundy, M.D., PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00644514
- Sponsor's protocol ID
- Pro00001166
- Other IDs
- Pro00001166, 12496-CP-001A
- Status last verified
- Jul 2013
- First submitted
- 24 Mar 2008
- Last updated
- 16 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Genetics of Environmental Asthma: LPS Inhalation and Bronchoscopy in Normal Subjects and Subjects With Mild Atopic Asthma
- ClinicalTrials.gov ID
- NCT00644514
- Acronym / sponsor ID
- Pro00001166
- Conditions
- Atopic Asthma, Healthy
- Keywords
- LPS endotoxin, Asthma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: grant funding no longer available
- Enrolment
- 17 participants (actual)
- Lead sponsor
- John SundyUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 26 Mar 2008 (estimated)
- Results
- Not posted in the source record
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 mediators and genes in airway epithelial and BAL cells that are differentially regulated following inhalation of endotoxin lipopolysaccharide (LPS) among study participants with allergic asthma and normal phenotypes. This approach is designed to identify novel genes associated with both asthma pathogenesis and asthma susceptibility. LPS, or endotoxin, a cell wall component of gram-negative bacteria, is ubiquitous in the environment, and is thought to influence both susceptibility and severity of asthma.
240 subjects (healthy adult men and women (age >18-40) with and without atopy and asthma) will complete the screening evaluations in order to establish 3 study groups of 60 subjects each. Each qualified subject will undergo an inhaled LPS endotoxin challenge followed by bronchoscopy after 24 hours, which will consist of a bronchoalveolar lavage (BAL) and endobronchial brush biopsies. BAL involves squirting a small amount of sterile salt water into one of the airways then gently taking it back out through the bronchoscope. The brush sample involves gently moving a small brush back and forth in an airway to collect cell samples. Samples of whole blood will also be obtained at various time points. RNA will be isolated from these cell populations in order to assess differential gene expression expression using microarrays.
Detailed description
Background:
Endotoxin or lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, is ubiquitous in the environment, and is often present in high concentrations in organic dusts, as well as in air pollution, and household dusts. There is convincing evidence that endotoxin exacerbates airflow obstruction and airway inflammation in allergic asthmatics. Additional findings indicate that allergic airways can enhance the response to inhaled endotoxin, and that endotoxin can enhance the airway response to allergens. However, when considering the interaction between endotoxin and allergens, the timing of the exposure appears to be critical. Emerging evidence suggests that early exposure to endotoxin, a potent inducer of Th1 type cytokines (IFN-g and IL-12), may minimize the risk of allergen sensitization which could has profound effects on reducing the risk of developing asthma in children. Independent of its effect in allergic asthma, several studies demonstrate that inhalation of air contaminated with endotoxin is associated with the classical features of asthma (reversible airflow obstruction and airway inflammation, and persistent airway hyperreactivity and airway remodeling). Epidemiological studies have shown that the concentration of inhaled endotoxin in the bioaerosol is strongly and consistently associated with reversible airflow obstruction among cotton workers, agricultural workers, and fiberglass workers. Importantly, the concentration of endotoxin in the bioaerosol is the most important occupational exposure associated with the development and progression of airway disease in agricultural workers. Experimentally, inhalation of endotoxin can cause reversible airflow obstruction and airway inflammation in previously unexposed healthy study subjects. The ability of the host to respond to endotoxin is highly variable, and is influenced in part by genetic factors.:
The rationale for this investigation is based on the following points:
- asthma is caused in large part by both genetic susceptibility and environmental exposure,
- a variety of immune and non-immune mechanisms can function independently or interactively to cause airway hyper-reactivity, airflow obstruction, airway inflammation, and airway remodeling,
- environmental challenges can be used to "narrow the asthma phenotype" and allow one to investigate unique gene-environment interactions that are involved in the development of biologically specific forms of asthma,
- genes that are over or under stimulated in the airway epithelia of asthmatics following inhalation challenge are important in the pathogenesis of asthma
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LPS endotoxin inh f/u bronchoscopy | Experimental | Biological: Endotoxin - lipopolysaccharide (LPS)Participants receive inhalation of LPS endotoxin, followed by bronchoscopy in this study. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Allergic asthmatic, allergic non-asthmatic, or nonallergic nonasthmatic
- Willing/able to give informed consent \& adhere to visit/protocol schedules.
- Screening visit laboratory, C-Xray, EKG, results within normal limits
- Women of childbearing potential must have a negative serum pregnancy test
- Screening Pulmonary function testing above study criteria parameters
Key exclusion criteria (16 listed)
- Systemic corticosteroid administration for asthma within the previous 90days
- Antibiotic administration within the previous 30 days.
- Viral respiratory infection within the previous 14 days.
- History of severe asthma requiring intubation.
- Occupational exposure to hay or grain dust.
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 |
|---|---|---|
| Endotoxin - lipopolysaccharide (LPS)Also: Lipopolysaccharide (LPS), NIH Clinical Center Reference EndotoxinNebulized 5000EU, 10,000EU, 20,000EU endotoxin doses delivered to completion. Nebulized dose inhaled 30 minutes apart if no adverse events occur after the previous dose. Fiberoptic Bronchoscopy with Bronchoalveolar Lavage (BAL) and brush samples performed 24 hours after LPS nebulization. | Biological | LPS endotoxin inh f/u bronchoscopy |
Primary outcome
Identify Genes in airway epithelial and Bronchoalveolar Lavage (BAL)that are differentially regulated following inhalation of LPS endotoxin.
Time frame: bronchoscopy performed 24 hours after inhalation of endotoxin
1 secondary outcome
Identify mediators in airway epithelial and BAL cells that are differentially regulated following LPS inhalation.
Time frame: Bronchoscopy performed 24 hours post inhalation of endotoxin
Results and safety
The study was stopped early (reason given: grant funding no longer available). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2013.
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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 S Sundy, M.D., PhD principal investigator
Duke University
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 Endotoxin - lipopolysaccharide (LPS) in people with Atopic Asthma and Healthy, run by John Sundy 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 16 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: stopped early, as of the sponsor's last update on 16 Jul 2013. 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?
The study was stopped early (reason given: grant funding no longer available). Results are not available in the source record.
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?
Identify Genes in airway epithelial and Bronchoalveolar Lavage (BAL)that are differentially regulated following inhalation of LPS endotoxin. (time frame: bronchoscopy performed 24 hours after inhalation of endotoxin). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jul 2013.