COPDNCT01974154
COPD Metabolome, Smoking Oxidants and Aberrant Ciliated Cell Function
An observational study of COPD and Smoking, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD), the 4th cause of mortality in the US. Central to COPD pathogenesis is "ciliopathy", dysfunction of the airway ciliated cells that mediate transport of mucus to remove inhaled pathogens. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- What is being tested?
- Cohort I and Cohort II
- How many people
- 206 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to May 2019
- Phase
- Observational
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: New York Metropolitan area residents
Who may be able to join
- All study subjects should be able to provide informed consent Males or females ages 18 years and older Must provide HIV informed consent Lung disease proven by at least one of the following: symptoms consistent with pulmonary disease; (2) chest X-rays consistent with lung disease; (3) pulmonary function tests consistent with lung disease; (4) lung biopsy consistent with lung disease; (5) family history of lung disease; and/or (6) diseases of organs with known association with lung disease
Who cannot join
- Individuals not deemed in good overall health by the investigator will not be accepted into the study.
- Habitual use of drugs and/or alcohol within the past six months (Acceptable: Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria).
- Individuals with history of chronic lung disease, including asthma or with recurrent or recent (within three months) acute pulmonary disease will not be accepted into the study.
- Individuals with allergies to atropine or any local anesthetic will not be accepted into the study.
- Individuals with allergies to pilocarpine, isoproterenol, terbutaline, atropine or aminophylline will not be accepted into the study.
- Females who are pregnant or nursing will not be accepted into the study Any history of allergies to xylocaine, lidocaine, versed, valium, atropine, pilocarpine, isoproterenol, terbutaline, aminophylline, or any local anesthetic will not be included in the study Patient refuses consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Cornell Medical College - Department of Genetic Medicine
New York, New York, 10021
About this study
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD), the 4th cause of mortality in the US. Central to COPD pathogenesis is "ciliopathy", dysfunction of the airway ciliated cells that mediate transport of mucus to remove inhaled pathogens. The focus of this study is to carry out metabolic profiling of banked biologic samples and assess the hypothesis that COPD is associated with a unique metabolome in serum and lung epithelial lining fluid, and that subsets of the COPD metabolome are linked to the ciliopathy of COPD.
Read the detailed description
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD), the 4th cause of mortality in the US. Central to COPD pathogenesis is "ciliopathy", dysfunction of the airway ciliated cells that mediate transport of mucus to remove inhaled pathogens. The COPD ciliopathy leads to mucus accumulation, impaired host defense and recurrent infections. Using a state-of-the-art platform for global metabolite profiling and unique cohorts with serum and lung biologic samples, our deliverables are to identify a metabolome focused on biomarkers related to airway ciliopathy in COPD, and use the observed metabolic changes to: (1) direct mechanistic studies to define ciliopathy at a molecular level; (2) identify novel targets for therapeutic intervention in COPD; and (3) identify smokers at high risk for COPD. Preliminary metabolic data led to our first clues - COPD smokers have decreased serum citrulline levels, consistent with a deficiency in lung nitric oxide synthase (NOS) activity, and thus lung nitric oxide (NO) deficiency. This, together with supporting data of a smoking-induced NOS/NO-related ciliopathy, and knowledge that smokers have significant oxidant-related changes in the airway epithelial transcriptome, led to our aims, combining metabolomics of defined cohorts, murine and human mechanistic studies and computational / statistical integration.
Aim 1. To carry out metabolic profiling of banked biologic samples of our characterized cohorts to assess the hypothesis that COPD is associated with a unique metabolome in serum and lung epithelial lining fluid, and that subsets of the COPD metabolome are linked to the ciliopathy of COPD.
Aim 2. To combine metabolic profiling and in vitro studies of human and murine airway epithelium to evaluate the hypothesis that there is a link between the COPD metabolome (focusing on the inferred NO deficiency) and mechanisms underlying the ciliopathy of COPD.
Aim 3. Characterize and quantify the cigarette smoke induced "redoxome" in lung and serum and assess its role in ciliated cell dysfunction. Studies seek to identify a link between smoking, a burden of oxidants to the lung epithelium and the pathogenesis of COPD - potentially providing biomarker(s) that predict which smokers will develop COPD and identifying new targets for therapy of COPD.
- Being tested
- Cohort I, Cohort II
- Keywords
- COPD, Smoking, Non-smoker
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cohort IOther
We will evaluate serum and lung ELF obtained by bronchoalveolar lavage, under previous protocols, from 159 individuals at baseline and at 0, 3, 6 and 12 months.
Cohort IIOther
Quantify the cilia length on prepared slides from 67 cohort II samples of airway epithelium from biological samples were already obtained from subjects who were consented to participate in prior WCMC IRB approved protocols.
| Study group | Role | What they receive |
|---|---|---|
| Cohort I | A. Healthy nonsmokers B. Healthy smokers C. Healthy smokers/quit smoking D. COPD smokers E. COPD smokers/ quit smoking Receives: Other: Cohort I | |
| Cohort II | A. Smokers with normal spirometry and normal DLCO B. Smokers, normal spirometry, low DLCO Receives: Other: Cohort II |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gene expression changes in airway epithelium
We will perform metabolic profiling of biologic samples to assess the hypothesis that smoking-induced COPD is associated with a unique metabolome in serum and lung ELF, and that subsets of the COPD metabolome are linked to the ciliopathy of COPD.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2013 (estimated)
- Study startDec 2013
- Primary completionMay 2019
- Study completionMay 2019
Why it stopped: Lack of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPDStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 206 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ronald G Crystal, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01974154
- Sponsor's protocol ID
- 1305013966
- Other IDs
- RFA-HL-12-009
- Status last verified
- Jul 2020
- First submitted
- 25 Oct 2013
- Last updated
- 30 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COPD Metabolome, Smoking Oxidants and Aberrant Ciliated Cell Function
- ClinicalTrials.gov ID
- NCT01974154
- Acronym / sponsor ID
- 1305013966
- Keywords
- COPD, Smoking, Non-smoker
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Lack of funding.
- Enrolment
- 206 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Study start
- Dec 2013 (actual)
- Primary completion
- May 2019 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 1 Nov 2013 (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.
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD), the 4th cause of mortality in the US. Central to COPD pathogenesis is "ciliopathy", dysfunction of the airway ciliated cells that mediate transport of mucus to remove inhaled pathogens. The focus of this study is to carry out metabolic profiling of banked biologic samples and assess the hypothesis that COPD is associated with a unique metabolome in serum and lung epithelial lining fluid, and that subsets of the COPD metabolome are linked to the ciliopathy of COPD.
Detailed description
Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD), the 4th cause of mortality in the US. Central to COPD pathogenesis is "ciliopathy", dysfunction of the airway ciliated cells that mediate transport of mucus to remove inhaled pathogens. The COPD ciliopathy leads to mucus accumulation, impaired host defense and recurrent infections. Using a state-of-the-art platform for global metabolite profiling and unique cohorts with serum and lung biologic samples, our deliverables are to identify a metabolome focused on biomarkers related to airway ciliopathy in COPD, and use the observed metabolic changes to: (1) direct mechanistic studies to define ciliopathy at a molecular level; (2) identify novel targets for therapeutic intervention in COPD; and (3) identify smokers at high risk for COPD. Preliminary metabolic data led to our first clues - COPD smokers have decreased serum citrulline levels, consistent with a deficiency in lung nitric oxide synthase (NOS) activity, and thus lung nitric oxide (NO) deficiency. This, together with supporting data of a smoking-induced NOS/NO-related ciliopathy, and knowledge that smokers have significant oxidant-related changes in the airway epithelial transcriptome, led to our aims, combining metabolomics of defined cohorts, murine and human mechanistic studies and computational / statistical integration.
Aim 1. To carry out metabolic profiling of banked biologic samples of our characterized cohorts to assess the hypothesis that COPD is associated with a unique metabolome in serum and lung epithelial lining fluid, and that subsets of the COPD metabolome are linked to the ciliopathy of COPD.
Aim 2. To combine metabolic profiling and in vitro studies of human and murine airway epithelium to evaluate the hypothesis that there is a link between the COPD metabolome (focusing on the inferred NO deficiency) and mechanisms underlying the ciliopathy of COPD.
Aim 3. Characterize and quantify the cigarette smoke induced "redoxome" in lung and serum and assess its role in ciliated cell dysfunction. Studies seek to identify a link between smoking, a burden of oxidants to the lung epithelium and the pathogenesis of COPD - potentially providing biomarker(s) that predict which smokers will develop COPD and identifying new targets for therapy of COPD.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort I | – | Other: Cohort IA. Healthy nonsmokers B. Healthy smokers C. Healthy smokers/quit smoking D. COPD smokers E. COPD smokers/ quit smoking |
| Cohort II | – | Other: Cohort IIA. Smokers with normal spirometry and normal DLCO B. Smokers, normal spirometry, low DLCO |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- New York Metropolitan area residents
Key inclusion criteria (1 listed)
- All study subjects should be able to provide informed consent Males or females ages 18 years and older Must provide HIV informed consent Lung disease proven by at least one of the following: symptoms consistent with pulmonary disease; (2) chest X-rays consistent with lung disease; (3) pulmonary function tests consistent with lung disease; (4) lung biopsy consistent with lung disease; (5) family history of lung disease; and/or (6) diseases of organs with known association with lung disease
Key exclusion criteria (6 listed)
- Individuals not deemed in good overall health by the investigator will not be accepted into the study.
- Habitual use of drugs and/or alcohol within the past six months (Acceptable: Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria).
- Individuals with history of chronic lung disease, including asthma or with recurrent or recent (within three months) acute pulmonary disease will not be accepted into the study.
- Individuals with allergies to atropine or any local anesthetic will not be accepted into the study.
- Individuals with allergies to pilocarpine, isoproterenol, terbutaline, atropine or aminophylline will not be accepted into the study.
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 |
|---|---|---|
| Cohort IWe will evaluate serum and lung ELF obtained by bronchoalveolar lavage, under previous protocols, from 159 individuals at baseline and at 0, 3, 6 and 12 months. | Other | Cohort I |
| Cohort IIQuantify the cilia length on prepared slides from 67 cohort II samples of airway epithelium from biological samples were already obtained from subjects who were consented to participate in prior WCMC IRB approved protocols. | Other | Cohort II |
Primary outcome
Gene expression changes in airway epithelium
Time frame: One year
We will perform metabolic profiling of biologic samples to assess the hypothesis that smoking-induced COPD is associated with a unique metabolome in serum and lung ELF, and that subsets of the COPD metabolome are linked to the ciliopathy of COPD.
Results and safety
The study was stopped early (reason given: Lack of funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2020.
- Individual participant dataSharing planned: Undecided
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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.
Ronald G Crystal, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COPD and Smoking, run by Weill Medical College of Cornell University 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 1 inclusion and 6 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 30 Jul 2020. 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.
Are results available for this study?
The study was stopped early (reason given: Lack of funding.). 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?
Gene expression changes in airway epithelium (time frame: One year). 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 30 Jul 2020.