The Natural History of Gene Expression in the Lung Cells of Non-Smokers, Smokers and Ex-Smokers in Health and Disease
24. Juli 2020 aktualisiert von: Weill Medical College of Cornell University
The Natural History of Gene Expression in Lung Cells of Non-Smokers, Smokers, and Ex-Smokers in Health and Disease
Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD, commonly known as chronic bronchitis and emphysema).
Despite this clear link, only 15-20% of smokers develop COPD suggesting that genetic factors affect the lung's susceptibility to the stress of cigarette smoke.
The cells lining the airways (epithelium) and cells that help defend the lung (alveolar macrophages) of smokers develop gene expression changes that are different from that of nonsmokers.
In the investigators' previous studies they have demonstrated that there are greater than 200 genes that are responsive to cigarette smoke in these cells.
But the investigators do not know whether the gene expression is static or changes as a function of time.
Genes that show significant changes over time may be relevant to the progression of the disease.
Even though quitting smoking reduces the rate at which the lungs decline, many-smokers still go on to develop COPD.
This study will provide insights into the natural history of smoking-related gene expression of the lung cells in health and disease.
Studienübersicht
Status
Abgeschlossen
Detaillierte Beschreibung
Cigarette smoke is responsible for the majority of lung cancers and is the major cause of COPD, the fourth leading cause of death in the United States.
Despite the well established causal role of cigarette smoking in lung cancer and COPD, only 10-20% of smokers actually develop these diseases.
This suggests that there are genetic predisposing factors that place some individuals at greater risk.
Our prior work shows that healthy smokers (cigarette smokers with normal history, physical exam, lung function tests and chest x-rays) and smokers with COPD have marked up and down regulation of greater than 200 genes in the small airway epithelium and alveolar macrophages.
There is however, a varied response to smoking among individuals, with some individuals abnormally expressing far fewer genes.
The focus of this study is to evaluate the hypothesis that the response of the lung cells to the stress of smoking is unique to each individual but is consistent over time.
Furthermore, individuals that stop smoking will each have a unique response, but is constant over time for each individual.
By defining the patterns of biologic response over time among smoking, ex-smoking and nonsmoking subjects, we will be able to identify common biologic pathways as potential targets for intervention.
Studientyp
Beobachtungs
Einschreibung (Tatsächlich)
171
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
New York
-
New York, New York, Vereinigte Staaten, 10065-4870
- Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Ja
Studienberechtigte Geschlechter
Alle
Probenahmeverfahren
Nicht-Wahrscheinlichkeitsprobe
Studienpopulation
New York Metropolitan area residents
Beschreibung
Inclusion Criteria:
Group A: Healthy nonsmokers
- All study individuals should be enrolled in the "Airway" protocol #1204012331 "Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies"
- Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Never smokers is defined as someone who has smoked < 100 cigarettes per lifetime and whose urine nicotine <2 ng/mL and/or urine cotinine <5 ng/mL, at entry into the study
Group B: Healthy current smokers Inclusion:
- All study individuals should be enrolled in the "Airway" protocol
- Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Active smoker as evidenced by self-report and urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL
Group C: Healthy smokers who elect to stop smoking Inclusion:
- All study individuals should be enrolled in the "Airway" protocol
- Willing and able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Current smoker as evidenced by self-report and urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL
- Be a current smoker willing to stop smoking
Group D - Current smokers with COPD Inclusion:
- All study subjects will be enrolled in the "Airway" protocol #1204012331 "Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies"
- All study subjects should meet the lung disease criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure
- All study subjects should be able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Active smokers as evidenced by urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL
Group E - Current smokers with COPD who elect to stop smoking Inclusion:
- All study subjects will be enrolled in the "Airway" protocol #1204012331 "Collection of Airway, Blood and/or Urine Specimens from Subjects for Research Studies"
- All study subjects should meet the lung disease criteria for having COPD may be of any stage (GOLD I - IV), be ambulatory and have no evidence of respiratory failure
- All study subjects should be able to provide informed consent for the long term follow up study with repeated bronchoscopies
- Male and Female subject ≥18 years of age
- Active smokers as evidenced by urine nicotine >30 ng/mL and/or urine cotinine >50 ng/mL
- Be a current smoker willing to stop smoking
Exclusion Criteria:
Groups A - E
- Individuals unable to provide proper informed consent
- 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 asthma and with recurrent or recent (within three months) and/or acute pulmonary infection
- Individuals with allergy to lidocaine
- Significant kidney disease or subjects on dialysis
- Females who are pregnant or lactating or intending to become pregnant in the next 12 months
- Subjects who are HIV positive
- Subjects that have unstable coronary artery disease as evidenced by unstable angina, >Class II New York Heart Association (NYHA) cardiac status, history of congestive heart failure or MI within the last 12 months
- Subjects who are contraindicated for undergoing bronchoscopy
- Subjects having any medical condition that in the opinion of the investigator would preclude the subject from entering the study
Groups D and E
- Subjects may not have evidence of respiratory failure such as SpO2 <90% or PaO2 <60 mmHg
Groups C and E
- Current major depression or other significant psychiatric disorder
- Subjects currently taking anti-depressant medication
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
Kohorten und Interventionen
Gruppe / Kohorte |
|---|
|
A-Healthy Non smokers
Healthy nonsmokers.
Defined as non-smokers by self report and urine cotinine levels consistent with a nonsmoker (urine cotinine <5 ng/mL).
|
|
B-Healthy smoker
Healthy current smokers.
Subjects categorized as healthy according to criteria under "Collection" (#1204012331) protocol.
|
|
C-Healthy smoker to quit
Healthy smokers willing to quit.
Defined by self-report and urine cotinine levels consistent with an active smoker (urine cotinine >50 ng/mL).
|
|
D-Current smoker w. COPD
Current smokers with COPD.
COPD as defined by the GOLD criteria and currently smoking as defined by self-report and urine cotinine levels consistent with an active smoker (urine cotinine >50 ng/mL)
|
|
E-Current COPD smoker to quit
Current smokers with COPD willing to stop smoking.
Subjects have COPD as defined by the GOLD criteria
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Evaluate gene expression over time
Zeitfenster: 12/31/2013
|
To prospectively assess changes in lung cell gene expression over time in healthy nonsmokers, healthy smokers and smokers with COPD.
To examine what smoking-induced gene expression changes occur in the lung cells of healthy smokers and COPD smokers over time in response to cessation of smoking.
|
12/31/2013
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Quitters who return to smoking and the effects on gene expression
Zeitfenster: 12/31/2012
|
In individuals who quit but start smoking again despite the standard smoking cessation therapy, what are the effects on gene expression of returning to smoking.
To assess whether baseline gene expression determines what genes rapidly change to a more "normal" expression pattern with smoking cessation.
Does having established COPD determine the relative reversibility of the gene expression pattern with smoking cessation compared to healthy smokers.
|
12/31/2012
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
1. August 2009
Primärer Abschluss (Tatsächlich)
1. Juni 2013
Studienabschluss (Tatsächlich)
1. Juni 2013
Studienanmeldedaten
Zuerst eingereicht
9. September 2009
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
9. September 2009
Zuerst gepostet (Schätzen)
10. September 2009
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
27. Juli 2020
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
24. Juli 2020
Zuletzt verifiziert
1. Juli 2020
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 0905010391
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
UNENTSCHIEDEN
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .