The goal of this study is to develop a novel study design to safely and ethically conduct a long-term randomized controlled trial among patients at high risk for both sleep apnea and cardiovascular events that will examine whether effective positive airway pressure(PAP) therapy reduces cardiovascular risk. Patients with transient ischemic attack(TIA) or stroke have a high prevalence of sleep apnea(60-80%), and they are at high risk of cardiovascular events(myocardial infarction, congestive heart failure, recurrent stroke, and cardiovascular death)in the first year post event, despite current prevent strategies. Therefore, the treatment of sleep apnea may represent a novel therapeutic target to reduce cardiovascular outcomes in this high risk population.
The proposed study is a randomized controlled trial among patients with transient ischemic attack (TIA) and minor stroke, comparing strategies for the diagnosis and treatment of sleep apnea with usual care over 6-12 months at 2 sites (Yale University School of Medicine and Indiana University School of Medicine). Patients with TIA and minor stroke will be randomly assigned to either usual care or a diagnosis and treatment approach that includes ambulatory polysomnography and initiation of autotitrating CPAP for sleep apnea in a 1:2 (control:intervention) randomization scheme. Intervention patients with sleep apnea will receive either a standard CPAP treatment intervention or an enhanced protocol designed to increase long-term CPAP adherence. The primary outcomes will include: (a) the impact of CPAP on pathophysiologic markers in the following domains of cardiovascular risk: inflammation (CRP, Il-6), heightened sympathetic activity/parasympathetic withdrawal (plasma catecholamines and heart rate variability (HRV)), insulin resistance (HOMA-IR, HbA1C), endothelial injury (flow mediated vasodilation), and atherosclerosis (carotid intima-media thickness); and (b) long-term (6-12 month) CPAP adherence.
- CPAP machine and enhanced intervention Behavioral
Intervention Desc: Participants received CPAP machine plus targeted education and a behavioral adherence intervention ARM 1: Kind: Experimental Label: Enhanced Intervention Description: This group has unattended sleep study, increased CPAP support,behavioral adherence intervention, in person visits for 1 month, 6 month and regular phone contacts
- CPAP and standard intervention Device
Intervention Desc: Participants receive CPAP machine and education ARM 1: Kind: Experimental Label: Standard Intervention group Description: This group gets unattended sleep study, auto titrating CPAP, CPAP support, 1 in person visit and 4 phone contacts
- Standard CPAP Intervention Device
ARM 1: Kind: Experimental Label: Standard Intervention group Description: This group gets unattended sleep study, auto titrating CPAP, and standard CPAP support.
- Enhanced CPAP Intervention Behavioral
ARM 1: Kind: Experimental Label: Enhaced CPAP intervention Description: This group gets an unattended sleep study, autotitrating CPAP, and enhanced CPAP support.
- Allocation: Randomized
- Masking: Single Blind (Investigator)
- Purpose: Treatment
- Endpoint: Efficacy Study
- Intervention: Parallel Assignment
|Type||Measure||Time Frame||Safety Issue|
|Primary||Change in Inflammation Markers||Change from baseline to 12 months||No|
|Primary||Change in Autonomic Tone||Change from baseline to 12 months||No|
|Primary||Change in Metabolic Markers||Change from baseline to 12 months||No|
|Primary||Change in Atherosclerosis Indicators||Change from baseline to 12 months||No|
|Primary||Change in Endothelial Injury Indicators||Change from baseline to 12 months||No|
|Secondary||Determine level of CPAP adherence that correspond to improvements in markers of Cardiovascular risk||baseline to 1 year||No|
|Primary||Change in Cardiovascular Risk Markers||Change from baseline to end||No|
|Primary||determine the level of CPAP adherence that correspond to improvements in markers of Cardiovascular risk||Baseline to end of study||No|
|Secondary||Vascular event rate combination of stroke, acute coronary syndrome and all cause mortality||Baseline to end of study||No|
|Primary||To evaluate whether a diagnosis and treatment intervention strategy for sleep apnea results in a significant reduction in five domains of cardiovascular risk markers (inflammatory, autonomic, insulin resistance, endothelial, and atherosclerotic).||Change from baseline to final measurements (6-12 months)||No|
|Primary||To determine the level of CPAP adherence that corresponds to greatest improvements in markers of cardiovascular risk.||Change from baseline to final measurements (6-12 months)||No|
|Primary||To determine whether an enhanced intervention protocol (targeted education, customized cognitive intervention, increased CPAP support) will result in improved long-term CPAP adherence rates among patients with sleep apnea.||baseline to final measurements (6-12 months)||No|
|Secondary||To collect the vascular event rate as pilot data for a future effectiveness strategy trial of CPAP among patients with TIA and stroke to reduce cardiovascular events and death.||Baseline to final measurements (6-12 months)||No|
|Secondary||Examine the relationship between CPAP use and various domains of cardiovascular risk markers and the impact of sleep duration and sleep apnea severity.||baseline to final assessment (6-12 months)||No|
|Secondary||24 hour blood pressure measurements||basleine to final assessments (6-12 months)||No|