Cardiac Hemodynamics in Overlap Syndrome (COPD With Obstructive Sleep Apnea)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01261377
Recruitment Status : Withdrawn (the fellow interested in this project left the institution)
First Posted : December 16, 2010
Last Update Posted : January 12, 2017
Massachusetts General Hospital
Information provided by (Responsible Party):
Atul Malhotra, MD, Brigham and Women's Hospital

Brief Summary:
Patients with both sleep apnea and COPD have overlap syndrome, but their optimal management is not known. We plan to conduct a randomized trial of of bi-level PAP vs. night time oxygen to asses the impact of intervention on cardiac MRI and biomarkers.

Condition or disease Intervention/treatment Phase
Chronic Obstructive Airway Disease Device: Bi-level positive airway pressure (BPAP) Drug: Oxygen Device: CPAP Phase 1 Phase 2

Detailed Description:

Presence 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. Despite the high prevalence of overlap syndrome, little research has been done in this field. Overlap syndrome has been recently reported to have higher death rate than COPD alone, which is due to effect on the heart. However, the mechanisms by which overlap syndrome affects the heart are not known well. Also, the ideal treatment for overlap syndrome is not known.

This study is being done to find the mechanisms by which overlap syndrome affects the right and left sides of heart (using cardiac MRI to study the heart). We will also compare the effect of treatment with bi-level positive airway pressure device (BPAP) vs. night-time oxygen on heart in overlap syndrome. These aims will allow us to test the hypothesis that overlap syndrome patients have worse heart function than COPD only or OSA only, and treatment with BPAP device will improve the heart function better than oxygen only.

At the baseline visit, the subject will undergo an overnight sleep study in the hospital. In the morning, blood draw to measure serum inflammatory biomarkers (C-Reactive Protein, interleukin-6, P-selectin, ICAM-1, TNF-alpha), urine catecholamine level, six-minute walk test, questionnaire for health-related quality of life score and modified Medical Research Council (MMRC) dyspnea score, lung function tests, ultrasound of forearm blood vessels and cardiac MRI will be done. No follow-up visit is needed if the subject does not have sleep apnea. If the subject has sleep apnea based on the sleep study, he/she will be allotted to treatment with a BPAP device or night-time oxygen for 6 months. If the subject does not want to be treated with BPAP or oxygen, CPAP device will be used to treat sleep apnea. During the duration of study treatment, phone calls and a brief study visit at 3 months will be done to make sure there is no discomfort related to the treatment. After 6 months of study treatment, cardiac MRI, ultrasound of forearm blood vessels, lung function tests, blood draw for serum inflammatory biomarkers, urine catecholamine level, six-minute walk test, and questionnaires for dyspnea score and quality of life score will be repeated.

This study will help us in better understanding of mechanisms of high death rate due to effects on the heart in overlap syndrome. It will also help us in understanding better ways to treat sleep apnea in COPD patients.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of Effects of Bi-level Positive Airway Pressure Therapy and Nocturnal Oxygen Therapy on Right and Left Ventricular Hemodynamics in Overlap Syndrome (Co-existent Chronic Obstructive Airway Disease and Obstructive Sleep Apnea)
Study Start Date : November 2010
Actual Primary Completion Date : September 2011
Actual Study Completion Date : September 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Bi-level positive airway pressure (BPAP)
bi-level will be titrated to optimize oxygenation and ventilation.
Device: Bi-level positive airway pressure (BPAP)
The level of BPAP will be titrated to treat OSA as well as hypoxemia and hypercapnia. The duration of therapy will be six months.

Active Comparator: Nocturnal oxygen
oxygen will be provided as per standard of care.
Drug: 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.

Active Comparator: Continuous positive airway pressure
The level of CPAP will be titrated to treat OSA. The duration of therapy will be six months.
Device: CPAP
The level of CPAP will be titrated to treat OSA. The duration of therapy will be six months.

Primary Outcome Measures :
  1. Right ventricular end-diastolic volume [ Time Frame: Six months ]

Secondary Outcome Measures :
  1. Other cardiac hemodynamics parameters (end-systolic volume, ejection fraction, mass index and wall motion of right and left ventricles, coronary blood flow, pulmonary artery pressure and blood flow, etc.) [ Time Frame: Six months ]
  2. Serum inflammatory biomarkers (C-reactive protein, interleukin-6, ICAM-1 and P-selectin) [ Time Frame: Six months ]
  3. Urine catecholamine level [ Time Frame: Six months ]
  4. Flow mediated dilatation of brachial artery [ Time Frame: Six months ]
  5. Pulmonary Function tests [ Time Frame: Six months ]
  6. BODE Index [ Time Frame: Six months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Both men and women with age more than 18 years.
  • Known diagnosis of COPD (GOLD stage 2 or higher).

Exclusion Criteria:

  • Already using CPAP or BPAP device.
  • Estimated GFR <30 ml/min/1.73 m2 or on hemodialysis.
  • Women known to be pregnant or planning to be pregnant in next 6 months.
  • Cardiac pacemaker, metallic heart valves, metallic implants, claustrophobic.
  • Chronic atrial fibrillation or frequent premature ventricular contractions.
  • Using lipid-lowering medications, aspirin, oral steroids, steroid-sparing medications or anti-oxidant vitamin supplements.
  • If taking sildenafil or related drugs, unable to stop it within 48 hours of the study visit.
  • Contraindications to stress cardiac testing: acute myocardial infarction within 48 hours, unstable angina not yet stabilized with medical therapy, ongoing chest pain, active broncho-constriction, uncontrolled cardiac arrhythmia, symptomatic severe aortic stenosis, aortic dissection, acute pulmonary embolism or pericarditis.
  • Uncontrolled COPD or acute COPD exacerbation.
  • Known chronic inflammatory diseases like lupus or active infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01261377

United States, Massachusetts
Massachussets General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Massachusetts General Hospital
Principal Investigator: Atul Malhotra, MD Brigham and Women's Hospital

Responsible Party: Atul Malhotra, MD, Brigham and Women's Hospital Identifier: NCT01261377     History of Changes
Other Study ID Numbers: 2010-P001753
First Posted: December 16, 2010    Key Record Dates
Last Update Posted: January 12, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: nothing to include

Keywords provided by Atul Malhotra, MD, Brigham and Women's Hospital:
COPD, obstructive sleep apnea, OSA, BPAP, CPAP

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Nervous System Diseases
Lung Diseases