CPAP Therapy in Patients With Heart Failure and Obstructive Sleep Apnea.

NCT00756366 | Completed Phase 1

• 3 other identifiers: 2005982-01HHSFO #NA5665HSFO #T6426
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure affects approximately 5-6 million North Americans and is increasing in prevalence. Sleep-related disorders, such as obstructive sleep apnea (OSA) often coexist (11-37% incidence) with heart failure. OSA is the repeated temporary interruption of breathing during sleep and occurs when the air passages in the upper respiratory tract become blocked during sleep. OSA adversely affects the cardiovascular system resulting in hypoxia (decrease in oxygen supply), which decreases the oxygen supply to the heart. Patients with OSA are treated with continuous positive airway pressure (CPAP). It has also been shown that CPAP reduces angina during sleep, minimizes sympathetic nervous system (SNS) activation and improves left ventricular (LV) function, although the mechanism of action is not clear. Carbon-11 acetate PET imaging allows for the assessment of how the heart works and how efficiently the heart uses oxygen in certain circumstances. Carbon-11 hydroxyephedrine (HED) measures cardiac nervous system activity, which may have an effect on heart rate. The study will evaluate the term effects of continuous positive airway pressure (CPAP), a common treatment for patients with OSA, on the heart's efficiency or ability to work and its effect on the nervous system activity of the heart. Two patient groups will be evaluated 1.) patients with congestive heart failure and obstructive sleep apnea will be randomized to early or late CPAP to address the primary hypothesis of the study and 2.) patients with congestive heart failure only (matched control group). Both the primary randomized study group and secondary study group will be evaluated using \[11C\]acetate PET, \[11C\]HED PET and echocardiography. Measurements will be obtained at baseline, 1 week (where possible) and 6-8 weeks.

Conditions

Heart Failure; Obstructive Sleep Apnea

Keywords

positron emission tomography; myocardial energetics; sympathetic nerve function

Outcome Measures

Primary Outcomes (2)

• Measurements of oxidative metabolism (11C clearance rate constant 'k') and WMI

  The differences in the measurements of oxidative metabolism (11C clearance rate constant 'k') and WMI will be analyzed using t-tests for the treatment groups

  at 6-8 weeks

• C-11 Hydroxyephedrine (HED) retention

  C-11 HED retention will be a measure myocardial SN pre-synaptic function in treatment groups

  6-8 weeks

Secondary Outcomes (1)

• Changes in other parameters including New York Heart Association (NYHA) class, HR, BP, LV volumes, stroke work-index, and QoL scores will also be analyzed. The subgroups of ischemic and non-ischemic etiology will be analyzed

  at 6-8 weeks

Study Arms (3)

1

ACTIVE COMPARATOR

Heart Failure-OSA Group, randomized to early CPAP

Other: Positron Emission Tomography

2

ACTIVE COMPARATOR

Heart Failure-OSA Group, randomized to late CPAP

Other: Positron Emission Tomography

3

OTHER

Heart Failure- no OSA, no CPAP therapy, observational group

Other: Positron Emission Tomography

Interventions

Positron Emission Tomography OTHER

PET imaging at baseline, 1 week and 6-8 weeks. CPAP begins after baseline PET scan.

Also known as: PET

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• systolic LV dysfunction (LVEF\<40%; by echocardiography, radionuclide or contrast ventriculography)
• symptoms of HF: NYHA Class II to III
• stable condition with optimally tolerated medical therapy, unchanged for \> 4 weeks
• Obstructive sleep apnea (OSA) diagnosed on nocturnal polysomnogram with an apnea/hypopnea index (AHI) \>15 events/hr and a predominantly obstructive pattern(more than 80% of events being obstructive in nature)OR
• no OSA: defined as AHI\<5 (control subjects) will be matched with the OSA group for gender, age + 5 years, ejection fraction (EF) +5%, drug therapy and etiology of HF (ischemic or non-ischemic)
• willingness to receive CPAP therapy
• informed consent

You may not qualify if:

• unstable angina or recent myocardial infarction (MI) (\<4 weeks prior)
• severe valvular dysfunction
• requirement for revascularization
• a permanent pacemaker
• atrial fibrillation
• significant ventricular arrhythmia or sinus node dysfunction
• life expectancy less than 1 year due to other co-morbidity
• significant restrictive and obstructive lung disease
• concomitant treatment or use of: tricyclic antidepressants, cocaine or drugs which may alter catecholamine uptake; or hypnotic, benzodiazepine, selective serotonin reuptake inhibitors(SSRI), neuroleptic, narcotic or other medications which may alter sleep or sleep-disordered breathing
• central sleep apnea
• other primary sleep disorder (i.e. periodic limb movement with arousal \>5 events/hr, narcolepsy, rapid eye movement (REM) behaviour disorder)
• requiring supplemental oxygen therapy at night
• debilitating daytime somnolence (indicating clear-cut indication for CPAP therapy)
• a previous cardiac transplant
• a large transmural scar defined on previous perfusion imaging(severe resting perfusion defect (\<50% uptake) occupying \>25% of the LV)148-150

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead
• Heart and Stroke Foundation of Ontario: collaborator

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Related Publications (3)

• Hall AB, Ziadi MC, Leech JA, Chen SY, Burwash IG, Renaud J, deKemp RA, Haddad H, Mielniczuk LM, Yoshinaga K, Guo A, Chen L, Walter O, Garrard L, DaSilva JN, Floras JS, Beanlands RS. Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: a randomized study. Circulation. 2014 Sep 9;130(11):892-901. doi: 10.1161/CIRCULATIONAHA.113.005893. Epub 2014 Jul 3.

  PMID: 24993098 BACKGROUND

• Johnson CB, Beanlands RS, Yoshinaga K, Haddad H, Leech J, de Kemp R, Burwash IG. Acute and chronic effects of continuous positive airway pressure therapy on left ventricular systolic and diastolic function in patients with obstructive sleep apnea and congestive heart failure. Can J Cardiol. 2008 Sep;24(9):697-704. doi: 10.1016/s0828-282x(08)70668-8.

  PMID: 18787720 BACKGROUND

• Yoshinaga K, Burwash IG, Leech JA, Haddad H, Johnson CB, deKemp RA, Garrard L, Chen L, Williams K, DaSilva JN, Beanlands RS. The effects of continuous positive airway pressure on myocardial energetics in patients with heart failure and obstructive sleep apnea. J Am Coll Cardiol. 2007 Jan 30;49(4):450-8. doi: 10.1016/j.jacc.2006.08.059.

  PMID: 17258090 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Sleep Apnea, Obstructive

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Rob S Beanlands, MD, FRCP C

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Robert S Beanlands, MD, FRCPC, Chief of Cardiology

Study Record Dates

• First Submitted: September 18, 2008
• First Posted: September 22, 2008
• Study Start: July 1, 2005
• Primary Completion: June 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 30, 2018

Record last verified: 2018-05

Locations

CA (1)