Right Ventricular Hemodynamics Using Cardiac MRI in Patients COPD and OSA

Right Ventricular Hemodynamics Using Cardiac Magnetic Resonance Imaging in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Obstructive Sleep Apnea (OSA)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease; Obstructive Sleep Apnea; Overlap Syndrome
• Intervention / Treatment: Device: Bi-level positive airway pressure (BPAP); Drug: Nocturnal oxygen

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92093
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bi-level positive airway pressure (BPAP)	Device: Bi-level positive airway pressure (BPAP); 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.; Other Names: BPAP
Active Comparator: Nocturnal oxygen	Drug: Nocturnal 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.; Other Names: NOT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right Ventricular Remodeling Index	Defined as the ratio between RVMI and RV end-diastolic volume index using MRI	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right Ventricular Mass Index	MRI	Six months
Right Ventricular End Systolic and Diastolic Volume	MRI	Six months
Right Ventricular Ejection Fraction	MRI	Six months
Myocardial Extracellular Volume	MRI	Six months
Left Ventricular Remodeling Index	MRI	Six months
Left Ventricular Mass Index	MRI	Six months
Left Ventricular End Systolic and Diastolic Volume	MRI	6 months
Left Ventricular Ejection Fraction	MRI	6 months
Serum C-reactive Protein Level	blood test	6 months
Serum Tumor Necrosis Factor-alpha Level	blood test	6 months
Serum Interleukin-6 Level	blood test	6 months
Serum Intercellular Adhesion Molecule-1	blood test	6 months
Serum P-selectin Level	Blood test	6 months
Urine Catecholamine Level	Urine test	6 months
6 Minute Walk Distance	Low-grade physical activity test	6 months
Quality of Life Score Through St. George's Respiratory Questionnaire (SGRQ)	Questionnaire	6 months
Degree of Daytime Sleepiness Through Epworth Sleepiness Scale (ESS)	Questionnaire	6 months
Sleep Quality Through Pittsburgh Sleep Quality Index (PSQI)	Questionnaire	6 months
General Health Status Through Short Form 36 (SF-36) Health Survey	Questionnaire	6 months

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Robert L Owens, MD, UCSD

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: September 15, 2014
• First Submitted That Met QC Criteria: September 16, 2014
• First Posted (Estimate): September 19, 2014

Study Record Updates

• Last Update Posted (Actual): July 28, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: UCSD140959