Trial record 16 of 244 for:    sleep studies OR polysomnogram OR multiple sleep latency test OR maintenance of wakefulness test | Open Studies | NIH, U.S. Fed

Sleep Apnea in TIA/Stroke: Reducing Cardiovascular Risk With Positive Airway Pressure (Sleep Tight)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Yale University
Sponsor:
Collaborators:
Indiana University
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01446913
First received: October 3, 2011
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Transient Ischemic Attack
Stroke
Device: Standard CPAP Intervention
Behavioral: Enhanced CPAP Intervention
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: Sleep Apnea in TIA/Stroke: Reducing Cardiovascular Risk With Positive Airway Pressure

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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). [ Time Frame: Change from baseline to final measurements (6-12 months) ] [ Designated as safety issue: No ]
    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 catecholamine and heart rate variability (HRV)), insulin resistance (HOMA-IR), endothelial injury (flow mediated vasodilation), and atherosclerosis (carotid intima-media thickness). This analysis will include both an intention to treat analysis for all randomized patients as well as a pre-specified subgroup analysis of only patients with sleep apnea.

  • To determine the level of CPAP adherence that corresponds to greatest improvements in markers of cardiovascular risk. [ Time Frame: Change from baseline to final measurements (6-12 months) ] [ Designated as safety issue: No ]
    The comparison of change in biomarkers at the time of final measurement between CPAP adherence groups will be restricted to intervention patients with sleep apnea (both the enhanced protocol and the standard protocol patients). We will use mixed models with random effect of patients to test for differences among three CPAP adherence groups (good CPAP use, some CPAP use and no CPAP use, adjusting for follow-up length (in months) (possible interaction term of follow-up length and CPAP adherence groups), site, and TIA/stroke strata. If the overall estimate of the effect for adherence group is statistically significant, we will further assess the differences between pairs of groups (good CPAP use vs. some CPAP use, some CPAP use vs. no CPAP use, and good CPAP use vs. no CPAP use).

  • 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. [ Time Frame: baseline to final measurements (6-12 months) ] [ Designated as safety issue: No ]
    This analysis will be restricted to intervention patients with sleep apnea. We will compare the proportion of patients with good CPAP use in the enhanced versus standard protocols, using logistic regression adjusting for follow-up length (in months) (possible interaction term of follow-up length and treatment), site, and TIA/stroke strata. We will report the observed proportions with 95% confidence intervals.


Secondary Outcome Measures:
  • 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. [ Time Frame: Baseline to final measurements (6-12 months) ] [ Designated as safety issue: No ]
    We will report the observed vascular event rates (stroke, acute coronary syndrome, and all-cause mortality) in person years (and with 95% confidence intervals) in the intervention patients (both the enhanced protocol and the standard protocol patients) and the control patients. We will not compare these rates with stochastic testing given that this study has not been designed to provide adequate power for this comparison.

  • Examine the relationship between CPAP use and various domains of cardiovascular risk markers and the impact of sleep duration and sleep apnea severity. [ Time Frame: baseline to final assessment (6-12 months) ] [ Designated as safety issue: No ]
    This analysis will be restricted to (definite TIA/Stroke) intervention patients with sleep apnea. We will begin this exploratory analysis by graphing the association between CPAP use (on the x-axis) and the change in the cardiovascular markers (on the y-axis). For these graphical analyses, we will use the following measures of CPAP use: (a) total cumulative hours of CPAP use over the study period (continuous variable in hours); (b) the mean observed hours of CPAP use per night divided by the estimated average hours of sleep per night (continuous variable that ranges from 0 to 100%) (Figure 11). To establish the relationship between CPAP use and cardiovascular markers we may then engage in regression modeling, controlling for site, and TIA/stroke strata. Analyses will be conducted for all subjects, and by AHI severity groups (5-15, 15-30, ≥ 30).

  • 24 hour blood pressure measurements [ Time Frame: basleine to final assessments (6-12 months) ] [ Designated as safety issue: No ]
    We will use similar ANCOVA as in primary analysis plan to analyze: (a) mean 24-hour systolic, diastolic BP; (b) the defined daily dose (DDD) of antihypertensive medications (which is defined as the average maintenance dose per day for a drug used for its main indication in adults (http://www.whocc.no/atcdd/)); (c) medication-adjusted 24-hour SBP, which is calculated as [mean 24-hour SBP in mmHg] + [patient's DDD × (8.0 mmHg). We will also use a logistic regression model for the binary outcomes: (a) the patients with a dipping in systolic or diastolic BP ≥ 10% at follow-up or not; and (b) patients with a decrease from baseline to follow-up in 24-hour SBP of 5 mmHg or not, with the independent variables of baseline BP measurements, follow-up time, treatment arms, possible interaction term of time and treatment arms, and baseline characteristics which are clinically different between groups at baseline (p < 0.05).


Other Outcome Measures:
  • Patient-reported measurements [ Time Frame: baseline to final assessments (6-12 months) ] [ Designated as safety issue: No ]
    The analysis will be restricted to patients with sleep apnea. For patient-reported measurements (NIH stroke scale for all, stroke patients and TIA patients, modified Rankin score, Epworth sleepiness scale, and PHQ8), results are summarized by means (standard deviations) and medians (minimum, maximum) will be used. Mixed models will be used where the dependent variables are the measurements baseline and follow-up, and the independent variables are follow-up length (in months), treatment arm and possible interaction term of follow-up length (in months) and treatment arm adjusting for baseline measurement, site and TIA/stroke strata.

  • Safety Analyses [ Time Frame: baseline to final assessments (6-12 months) ] [ Designated as safety issue: Yes ]
    All adverse events will be reported regardless of severity and relationship to CPAP. The incidence of adverse events will be summarized with frequency tables by three treatment arms and receiving CPAP or not.


Estimated Enrollment: 255
Study Start Date: May 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard Intervention group
This group gets unattended sleep study, auto titrating CPAP, and standard CPAP support.
Device: Standard CPAP Intervention
Active Comparator: Enhaced CPAP intervention
This group gets an unattended sleep study, autotitrating CPAP, and enhanced CPAP support.
Behavioral: Enhanced CPAP Intervention
No Intervention: Usual Care
This group usual care after TIA/stroke and a sleep study at the end of the study.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years and older
  • TIA or ischemic stroke
  • within 1 week of neurological symptom onset
  • brain imaging within 24 hours

Exclusion Criteria:

  • known to have sleep apnea
  • suspected sleep disorder other than sleep apnea
  • hospice patients or patients receiving comfort only measures
  • patients unable to use a nasal or face mask
  • patients who require mechanical ventilation
  • Non English language patients
  • inability to provide informed consent
  • active suicidal ideation
  • live outside the recruitment area
  • provider does not allow researcher to contact patient
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01446913

Locations
United States, Connecticut
Yale University Completed
New Haven, Connecticut, United States, 06511
United States, Indiana
University of Indiana Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Curt Austin, BFA,MDiv    317-988-3152    curtaust@iupui.edu   
Principal Investigator: Dawn Bravata, MD         
Sponsors and Collaborators
Yale University
Indiana University
Investigators
Principal Investigator: Henry Yaggi, MD,MPH Yale University
Principal Investigator: Dawn M Bravata, M.D. Indiana University School of Medicine
  More Information

No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01446913     History of Changes
Other Study ID Numbers: 1101007811, U34HL105285-01
Study First Received: October 3, 2011
Last Updated: November 12, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Yale University:
Sleep Apnea
CPAP adherence
behavioral adherence
stroke

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Disorders, Intrinsic
Sleep Disorders
Apnea
Ischemic Attack, Transient
Stroke
Cerebral Infarction
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Dyssomnias
Brain Infarction

ClinicalTrials.gov processed this record on August 28, 2014