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Pathophysiology of the Upper Airway in Patients With COPD and Concomitant OSA

Primary Purpose

Obstructive Sleep Apnea

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Sleep and pulmonary physiologic measurements
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Obstructive Sleep Apnea focused on measuring Obstructive Sleep Apnea, Chronic Obstructive Pulmonary Disease, Overlap syndrome, Pcrit, Critical closing pressure

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for COPD Subjects:

  • Age range 40-70 years.
  • Demonstrated moderate to severe COPD as determined by spirometry (post-bronchodilator spirometry FEV1/FVC < 0.70 for diagnosing CODP and FEV1<80% predicted for staging)
  • Smoking history of ≥ 10 pack-years

Inclusion Criteria for Control Subjects

  • Age range 40-70 years
  • Demonstrated no COPD as determined by normal spirometry (post-bronchodilator spirometry FEV1/FVC > 0.70 for diagnosing CODP and FEV1<80% predicted for staging)
  • No smoking history as defined by less than 100 cigarettes smoked in a lifetime

Exclusion Criteria for both COPD and Control Subjects:

  • Metal objects that may interfere with chest CT quantification including presence of a cardiac pacemaker, defibrillator, metal prosthetic heart valve, metal projectile or metal weapon fragment (bullet, shrapnel, shotgun shot) or metal shoulder prosthesis
  • Subjects unable to perform spirometry due to:

    • chest or abdominal surgery in the past three months
    • a heart attack in the last three months
    • detached retina or eye surgery in the past three months
    • hospitalization for any other heart problem in the past month
  • History of hypersensitivity to Afrin, Lidocaine or albuterol
  • A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.
  • More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day
  • Pregnancy or suspected pregnancy

Sites / Locations

  • University of California, San Diego

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

COPD Group

Normal Control Group

Arm Description

Patients who were previously diagnosed of moderate to severe COPD as determined by spirometry. All patients will have sleep and pulmonary physiologic measurements.

Patients who are healthy, without major medical or sleep problems, and have normal spirometry. All patients will have sleep and pulmonary physiologic measurements.

Outcomes

Primary Outcome Measures

Critical closing pressure (PCrit)
Measured during overnight sleep study

Secondary Outcome Measures

Pharyngeal lavage cell count distribution
Minimal later airway dimension (mLAT)
Measured from upper airway CT scan
Minimal anteroposterior airway dimension (mAP)
Measured from upper airway CT scan
Minimal cross sectional airway area (mCSA)
Measured from upper airway CT scan
Lateral airway dimension on hard palate/uvula/epiglottis level
Measured from upper airway CT scan
Anteroposterior airway dimension on hard palate/uvula/epiglottis level
Measured from upper airway CT scan
Cross-sectional airway area on hard palate/uvula/epiglottis level
Measured from upper airway CT scan
Distance between the lower edge of the mandible and the lower edge of the hyoid (MH)
Measured from upper airway CT scan
Upper airway length
Measured from upper airway CT scan
Width of hard palate
Measured from upper airway CT scan
Nasophayngeal/retropalatal/retroglossal pharyngeal cavity volume
Measured from upper airway CT scan
Volume within the cervico-mandibular bony frame
Measured from upper airway CT scan
Volume of retropalatal/retroglossal soft tissue
Parapharyngeal fat pad volume
Tongue volume
Emphysema score
Measured from CT chest scan
Emphysema distribution
Measured from CT chest scan
Lower airway wall thickness on chest CT scan
Measured from CT chest scan
Forced expiratory volume in 1 second (FEV1)
Total lung capacity (TLC)
Ratio of residual volume / total lung capacity (RV/TLC)
Diffusing capacity of the lung for carbon monoxide (DLCO)

Full Information

First Posted
September 27, 2015
Last Updated
May 5, 2020
Sponsor
University of California, San Diego
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1. Study Identification

Unique Protocol Identification Number
NCT02567448
Brief Title
Pathophysiology of the Upper Airway in Patients With COPD and Concomitant OSA
Official Title
Pathophysiology of the Upper Airway in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Concomitant Obstructive Sleep Apnea (OSA)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Terminated
Why Stopped
Failed to accrue
Study Start Date
July 1, 2015 (Actual)
Primary Completion Date
August 11, 2016 (Actual)
Study Completion Date
August 11, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of study is to evaluate the physiologic effects of pulmonary tissue/structural changes associated with COPD and upper airway inflammation on upper airway collapsibility. Upper airway collapsibility is closely associated with development of obstructive sleep apnea (OSA), which is a common disease characterized by repetitive collapse of upper airway during sleep, leading to hypoxemia and arousal. OSA has important neurocognitive and cardiovascular consequences, especially in patients with COPD. Participants in this research study will undergo two overnight sleep studies (PSGs), pulmonary function test, and CT scan of the upper airway and chest. The first sleep study will evaluate the sleep breathing disorder and the second sleep study will measure the upper airway collapsibility, called critical closing pressure (Pcrit). Pcrit is measured by a modified continuous positive airway pressure (CPAP) machine which can provide a wide range of pressures between 20 and -20 cmH2O in order to modify upper airway pressure.
Detailed Description
This is a physiologic study to assess the effects of lower airway and lung tissue changes of COPD on upper airway collapsibility. Increased in lung volume and destruction of alveolar wall in COPD may have opposite and various effects on the upper airway collapsibility, which is an important factor of OSA development. Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are very common disorders associated with considerable morbidity, mortality, and healthcare costs. The prevalence of both co-existing conditions is estimated to be ~4% of the general population. This COPD-OSA "overlap" syndrome causes more severe hypoxemia than either COPD or OSA alone and has important clinical consequences, including death. COPD is usually excluded in OSA research and OSA is typically excluded or not assessed in studies of COPD; thus, available information about the "overlap" syndrome is limited. Therefore, it is important to identify patients with both COPD and OSA and determine the mechanisms of poor outcomes for these patients in order to optimize therapy. The pathophysiology of the COPD-OSA syndrome is not well understood. The investigators propose to investigate upper airway (UA) anatomic characteristics and collapsibility as potential underlying mechanisms that may help to explain the negative additive effect of having both conditions. The objectives are to study CT measures of airway anatomy and the critical closing pressure of the upper airway (Pcrit), a gold standard measure of upper airway collapsibility, in patients with COPD-OSA compared with COPD only and normal controls. CT scan of upper airway and chest will allow precise measures of upper airway characteristics and COPD associated alveolar and lower airway ch. angesMeasures of upper airway collapsibility will provide us information about the mechanical nature of the airway and if the patients are more likely to have OSA. Subjects with COPD-OSA may exhibit more upper airway inflammation possibly due to their pre-existing COPD disease and the reoccurring opening and closing of the upper airway due to the OSA. Therefore the investigators would like to assess the degree of inflammation in these patients compared to normal controls.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Sleep Apnea
Keywords
Obstructive Sleep Apnea, Chronic Obstructive Pulmonary Disease, Overlap syndrome, Pcrit, Critical closing pressure

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
COPD Group
Arm Type
Active Comparator
Arm Description
Patients who were previously diagnosed of moderate to severe COPD as determined by spirometry. All patients will have sleep and pulmonary physiologic measurements.
Arm Title
Normal Control Group
Arm Type
Active Comparator
Arm Description
Patients who are healthy, without major medical or sleep problems, and have normal spirometry. All patients will have sleep and pulmonary physiologic measurements.
Intervention Type
Other
Intervention Name(s)
Sleep and pulmonary physiologic measurements
Intervention Description
Two overnight sleep studies, CT scan of upper airway and chest, pulmonary function test and pharyngeal lavage
Primary Outcome Measure Information:
Title
Critical closing pressure (PCrit)
Description
Measured during overnight sleep study
Time Frame
Baseline
Secondary Outcome Measure Information:
Title
Pharyngeal lavage cell count distribution
Time Frame
Baseline
Title
Minimal later airway dimension (mLAT)
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Minimal anteroposterior airway dimension (mAP)
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Minimal cross sectional airway area (mCSA)
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Lateral airway dimension on hard palate/uvula/epiglottis level
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Anteroposterior airway dimension on hard palate/uvula/epiglottis level
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Cross-sectional airway area on hard palate/uvula/epiglottis level
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Distance between the lower edge of the mandible and the lower edge of the hyoid (MH)
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Upper airway length
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Width of hard palate
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Nasophayngeal/retropalatal/retroglossal pharyngeal cavity volume
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Volume within the cervico-mandibular bony frame
Description
Measured from upper airway CT scan
Time Frame
Baseline
Title
Volume of retropalatal/retroglossal soft tissue
Time Frame
Baseline
Title
Parapharyngeal fat pad volume
Time Frame
Baseline
Title
Tongue volume
Time Frame
Baseline
Title
Emphysema score
Description
Measured from CT chest scan
Time Frame
Baseline
Title
Emphysema distribution
Description
Measured from CT chest scan
Time Frame
Baseline
Title
Lower airway wall thickness on chest CT scan
Description
Measured from CT chest scan
Time Frame
Baseline
Title
Forced expiratory volume in 1 second (FEV1)
Time Frame
Baseline
Title
Total lung capacity (TLC)
Time Frame
Baseline
Title
Ratio of residual volume / total lung capacity (RV/TLC)
Time Frame
Baseline
Title
Diffusing capacity of the lung for carbon monoxide (DLCO)
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for COPD Subjects: Age range 40-70 years. Demonstrated moderate to severe COPD as determined by spirometry (post-bronchodilator spirometry FEV1/FVC < 0.70 for diagnosing CODP and FEV1<80% predicted for staging) Smoking history of ≥ 10 pack-years Inclusion Criteria for Control Subjects Age range 40-70 years Demonstrated no COPD as determined by normal spirometry (post-bronchodilator spirometry FEV1/FVC > 0.70 for diagnosing CODP and FEV1<80% predicted for staging) No smoking history as defined by less than 100 cigarettes smoked in a lifetime Exclusion Criteria for both COPD and Control Subjects: Metal objects that may interfere with chest CT quantification including presence of a cardiac pacemaker, defibrillator, metal prosthetic heart valve, metal projectile or metal weapon fragment (bullet, shrapnel, shotgun shot) or metal shoulder prosthesis Subjects unable to perform spirometry due to: chest or abdominal surgery in the past three months a heart attack in the last three months detached retina or eye surgery in the past three months hospitalization for any other heart problem in the past month History of hypersensitivity to Afrin, Lidocaine or albuterol A psychiatric disorder, other than mild depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders. More than 10 cups of beverages with caffeine (coffee, tea, soda/pop) per day Pregnancy or suspected pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xavier Soler, MD, PhD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States

12. IPD Sharing Statement

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Pathophysiology of the Upper Airway in Patients With COPD and Concomitant OSA

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