Chronic Obstructive Pulmonary Disease, Obstructive Sleep Apnea, Overlap Syndrome
Conditions
Brief summary
The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in the same patient has been termed overlap syndrome, affecting 1% of the U.S. population.The investigators propose to conduct this study that aims: (1) to compare right and left ventricular hemodynamic parameters using cardiac magnetic resonance imaging (MRI) in overlap syndrome vs. COPD only and OSA only; (2) to compare the effects of bi-level positive airway pressure (BPAP) vs. nocturnal oxygen therapy (NOT) on right ventricular (RV) hemodynamics in overlap syndrome. This study will allow us to test the hypothesis: (1) Patients with overlap syndrome have more RV dysfunction than those with COPD only or OSA only; (2) treatment of both hypoxemia and hypercapnia during sleep will improve RV hemodynamics compared with treatment of hypoxemia alone in patients with overlap syndrome.
Detailed description
Despite the high prevalence of overlap syndrome, few data are available on its pathophysiology and clinical consequences of these patients. Overlap syndrome has recently been reported to have excess cardiovascular mortality compared with COPD alone. However, no study has evaluated the mechanisms of excess cardiovascular mortality in untreated overlap syndrome. In addition, no prospective, randomized, controlled data are currently available on treatment of overlap syndrome. This study is divided into two parts. The first part (Part 1) is a cross-sectional cohort study comparing subjects with overlap syndrome to those with COPD alone and those with OSA alone. Patients with COPD and OSA overlap syndrome will be evaluated by an overnight sleep study, cardiac MRI, serum inflammatory biomarker, urine catecholamine level, pulmonary function test, and questionnaires of sleep and health related quality of life. These measurement will be compared between overlap syndrome and control groups with either COPD or OSA alone. The second part (Part 2) of the study is a prospective, parallel-group, randomized, controlled pilot study examining the effect of BPAP (and nocturnal oxygen if needed) vs. nocturnal oxygen therapy alone in patients with overlap syndrome (20 subjects in each treatment arm). The same measurement done during Part 1 will be repeated to evaluate the treatment effects.
Interventions
Overlap patients randomized to BPAP will be titrated as per American Academy of Sleep Medicine (AASM) guidelines and oxygen if needed based on saturations \<88% while on stable bi-level settings.
DRUGNocturnal oxygen
Oxygen will be titrated to keep resting oxygen saturation (as measured by pulse oximeter) more than 88 percent. The duration of therapy will be six months.
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Both men and women with age more than 18 years. * Known diagnosis of stable COPD (GOLD stage 2 or higher) or OSA.
Exclusion criteria
* Already using continuous positive airway pressure (CPAP), BPAP device, or nocturnal oxygen. * Known or suspected renal failure with estimated Glomerular filtration (GFR) \<50 ml/min/1.73 m2 or serum creatinine \> 1.5 mg/dl. * Chronic atrial fibrillation or frequent premature ventricular contraction (\> 10 beats per hour) * Women known to be pregnant or planning to be pregnant in next 6 months. * Known contraindication to MRI: cardiac pacemaker, metallic heart valves, metallic implants, history of claustrophobia. * If taking sildenafil or related drugs, unable to stop it within 48 hours of the study visit. * Uncontrolled COPD or acute COPD exacerbation. * Unstable cardiac diseases. * Known chronic inflammatory diseases like lupus or active infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Right Ventricular Remodeling Index | Six months | Defined as the ratio between RVMI and RV end-diastolic volume index using MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular End Systolic and Diastolic Volume | 6 months | MRI |
| Left Ventricular Ejection Fraction | 6 months | MRI |
| Serum C-reactive Protein Level | 6 months | blood test |
| Serum Tumor Necrosis Factor-alpha Level | 6 months | blood test |
| Serum Interleukin-6 Level | 6 months | blood test |
| Serum Intercellular Adhesion Molecule-1 | 6 months | blood test |
| Serum P-selectin Level | 6 months | Blood test |
| Urine Catecholamine Level | 6 months | Urine test |
| 6 Minute Walk Distance | 6 months | Low-grade physical activity test |
| Left Ventricular Mass Index | Six months | MRI |
| Degree of Daytime Sleepiness Through Epworth Sleepiness Scale (ESS) | 6 months | Questionnaire |
| Sleep Quality Through Pittsburgh Sleep Quality Index (PSQI) | 6 months | Questionnaire |
| General Health Status Through Short Form 36 (SF-36) Health Survey | 6 months | Questionnaire |
| Left Ventricular Remodeling Index | Six months | MRI |
| Right Ventricular Mass Index | Six months | MRI |
| Right Ventricular End Systolic and Diastolic Volume | Six months | MRI |
| Right Ventricular Ejection Fraction | Six months | MRI |
| Myocardial Extracellular Volume | Six months | MRI |
| Quality of Life Score Through St. George's Respiratory Questionnaire (SGRQ) | 6 months | Questionnaire |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chronic Obstructive Pulmonary Disease (COPD) Subjects with only Chronic Obstructive Pulmonary Disease (COPD). | 6 |
| Overlap Syndrome Subjects with simultaneous Obstructive Sleep Apnea (OSA) and Chronic Obstructive Pulmonary Disease (COPD). The dual diagnosis of these two conditions is referred to as Overlap Syndrome. | 16 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 |
Baseline characteristics
| Characteristic | Chronic Obstructive Pulmonary Disease (COPD) | Overlap Syndrome | Total |
|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 6.4 | 63.5 years STANDARD_DEVIATION 4.2 | 63.9 years STANDARD_DEVIATION 5.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 13 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 6 participants | 16 participants | 22 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 14 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 16 |
| other Total, other adverse events | 0 / 7 | 0 / 16 |
| serious Total, serious adverse events | 0 / 7 | 0 / 16 |
Outcome results
Primary
Right Ventricular Remodeling Index
Defined as the ratio between RVMI and RV end-diastolic volume index using MRI
Time frame: Six months
Population: one subject was dropped due to lack of efficacy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronic Obstructive Pulmonary Disease (COPD) | Right Ventricular Remodeling Index | 0.3747 ratio | Standard Deviation 0.06335 |
| Overlap Syndrome | Right Ventricular Remodeling Index | 0.2817 ratio | Standard Deviation 0.0363 |
Secondary
6 Minute Walk Distance
Low-grade physical activity test
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Degree of Daytime Sleepiness Through Epworth Sleepiness Scale (ESS)
Questionnaire
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
General Health Status Through Short Form 36 (SF-36) Health Survey
Questionnaire
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Left Ventricular Ejection Fraction
MRI
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Left Ventricular End Systolic and Diastolic Volume
MRI
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Left Ventricular Mass Index
MRI
Time frame: Six months
Population: No data collected as study was terminated prior to randomization
Secondary
Left Ventricular Remodeling Index
MRI
Time frame: Six months
Population: No data collected as study was terminated prior to randomization
Secondary
Myocardial Extracellular Volume
MRI
Time frame: Six months
Population: No data collected as study was terminated prior to randomization
Secondary
Quality of Life Score Through St. George's Respiratory Questionnaire (SGRQ)
Questionnaire
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Right Ventricular Ejection Fraction
MRI
Time frame: Six months
Population: No data collected as study was terminated prior to randomization
Secondary
Right Ventricular End Systolic and Diastolic Volume
MRI
Time frame: Six months
Population: No data collected as study was terminated prior to randomization
Secondary
Right Ventricular Mass Index
MRI
Time frame: Six months
Population: No data collected as study was terminated prior to randomization
Secondary
Serum C-reactive Protein Level
blood test
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Serum Intercellular Adhesion Molecule-1
blood test
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Serum Interleukin-6 Level
blood test
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Serum P-selectin Level
Blood test
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Serum Tumor Necrosis Factor-alpha Level
blood test
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Sleep Quality Through Pittsburgh Sleep Quality Index (PSQI)
Questionnaire
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization
Secondary
Urine Catecholamine Level
Urine test
Time frame: 6 months
Population: No data collected as study was terminated prior to randomization