Sleep Apnea Intervention for Cardiovascular Disease Reduction

NCT ID: NCT01261390

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 169 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2014-03-31

Brief Summary

Moderate to severe sleep apnea (a high number of breathing pauses on a sleep study) is a common health problem that is often associated with loud snoring and sleepiness.The medical term for this problem is obstructive sleep apnea (OSA). People with OSA often have an increased risk for developing heart disease or may already have a diagnosis of heart disease.

A clinical research study is being conducted at Brigham and Women's Hospital (BWH) and Beth Israel Deaconess Medical Center (BIDMC) to compare the effects of continuous positive airway pressure (CPAP) to conservative medical therapy with participation in one of four groups:

1. Active-PAP Therapy Group (Active-Beh or Active+Beh): Will receive standard medical treatment for sleep apnea with active-PAP. Participants will be randomized to either:

1. Active-Pap with respiratory therapist visits only

2. Active-Pap with respiratory therapist visits and cognitive behavioral therapist visits.

2. Alternative PAP Group (Sham): Will receive lower air delivery level than active-PAP therapy group. Will also have meetings with respiratory therapist.

3. Conservative Medical Therapy Group (CMT)*: Will receive a free supply of nasal strips for the duration of their treatment period (either 6 months or 12 months) and follow healthy sleep hygiene guidelines for how to change sleep habits to minimize incidences of apneas (breathing disturbances during sleep). Frequent follow-up support with research coordinator.

A sleep doctor or cardiologist will have indicated that a potential participant is an appropriate candidate to receive PAP or CMT as acceptable approaches to treat his/her sleep apnea. Participants will be recruited between the ages of 45-75 years who have diagnosed heart disease or between 55-75 years for those who have risk factors for developing heart disease.

This is a 6-12 month study** to evaluate alternative ways to address the potential for OSA treatment to reduce heart disease and to identify those features that would strengthen a later, large-scale randomized controlled trial.

We will test the hypothesis that active treatment for OSA with CPAP reduces CVD morbidity and mortality.

*All randomized participants will be given conservative medical therapy (CMT).

**For those randomized after December 31, 2012, follow-up assessment will only be 6 months long

Detailed Description

In this pilot randomized controlled trial, we will assess the effectiveness of CPAP therapy to reduce the burden of cardiovascular disease (CVD) and CVD risk factors in patients with moderate to severe obstructive sleep apnea (OSA) presenting to a sleep disorders clinic. A total of 700 patients with a new diagnosis of moderate to severe OSA will be recruited from BWH-affiliated sleep disorder clinics, BWH, Massachusetts General Hospital (MGH), and Faulkner Hospital Cardiology Clinics (and similar specialized clinics seeing patients with cardiovascular risk factors, such as endocrinology and hypertensive clinics), Beth Israel Deaconess Medical Center and Joslin Diabetes Center. After completing a 2 week run-in period, randomized participants (approximately 150 participants will be randomized) will undergo baseline and 6 month assessments of key study exposure and outcome variables.

Participants will be randomized after completion of Baseline visit. The treatment arms are as follows:

The active arms are:

1. Active-PAP treatment delivered using standard respiratory therapist (RT) adherence education and support. (Active-Beh)

2. Active-PAP treatment administered using adherence education and support delivered by a RT and enhanced by a behavioral promotion intervention. (Active+Beh)

The control arms are:

1. Conservative Medical Therapy (CMT)

2. Sham-PAP (Sham)

Participants randomized before December 31, 2012 (n=108) also will undergo 12 month follow-up assessments. Participants will be offered a 12 month supervised conservative medical therapy (CMT) program for OSA over the duration of the study intervention. Subjects would be contacted at bimonthly intervals by alternating phone and office visits to assess safety, identify adverse events, identify health care utilization, and reinforce protocol adherence. At 6 and 12 months, study outcomes will be reassessed by collecting data from sources.

Patients randomized after December 31, 2012 (n=61) will undergo only 6 months of follow-up assessment. Participants will be offered a 6 month supervised conservative medical therapy (CMT) program for OSA over the duration of the study intervention. Subjects would be contacted at bimonthly intervals by alternating phone and office visits to assess safety, identify adverse events, identify health care utilization, and reinforce protocol adherence. At 6 months, study outcomes will be reassessed by collecting data from sources.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Conservative Medical Therapy (CMT)

All participants will meet with a research assistant who will provide \~30 minutes of instruction on sleep hygiene and healthy lifestyle guidelines. Each subject's sleep routine will be reviewed with the aim to identify appropriate bed and wake times that provide a consistent schedule and allow for at least 7 hours of time in bed per night. Habits that may impact sleep, such as alcohol consumption, tobacco use, and exercise close to bedtime will be reviewed with appropriate guidance on how to minimize sleep disrupting exposures. Subjects will be provided external nasal dilator strips (Breath Right®) and advised on how to maximize sleep time in a non-supine position using bed elevation, wedge pillows and/or objects affixed to the back of their night clothes as appropriate.

Group Type: PLACEBO_COMPARATOR

Conservative Medical Therapy (CMT)

Intervention Type: BEHAVIORAL

All participants will meet with a research assistant who will provide 30 minutes of instruction on sleep hygiene and healthy lifestyle guidelines. Each subject's sleep routine will be reviewed with the aim to identify appropriate bed and wake times that provide a consistent schedule and allow for at least 7 hours of time in bed per night. Habits that may impact sleep, such as alcohol consumption, tobacco use, and exercise close to bedtime will be reviewed with appropriate guidance on how to minimize sleep disrupting exposures. Subjects will be provided external nasal dilator strips (Breathe Right®) and advised on how to maximize sleep time in a non-supine position using bed elevation, wedge pillows and/or objects affixed to the back of their night clothes as appropriate.

Sham PAP (Sham)

In addition to receiving CMT, participants in this treatment arm will receive a sham-CPAP unit. Sham devices look like active PAP devices, however, the exhalation port is increased and an orifice-resistor is inserted between the pump and tubing, creating a marginal pressure. A heated humidifier will be provided with this device and PAP masks will be fit and provided following the same procedures as for the active PAP arms.

The treatment visit schedule is outlined below.

1. PAP Initial Set-Up

2. 1-week follow up

3. 1-month follow up

4. 3-month follow up

5. 6-month follow up

6. 9-month follow up (will not occur if on a 6-month follow-up protocol)

It is estimated that each in-person follow-up adherence visit with the PAP specialist would last ~30 minutes.

Group Type: SHAM_COMPARATOR

Conservative Medical Therapy (CMT)

Intervention Type: BEHAVIORAL

All participants will meet with a research assistant who will provide 30 minutes of instruction on sleep hygiene and healthy lifestyle guidelines. Each subject's sleep routine will be reviewed with the aim to identify appropriate bed and wake times that provide a consistent schedule and allow for at least 7 hours of time in bed per night. Habits that may impact sleep, such as alcohol consumption, tobacco use, and exercise close to bedtime will be reviewed with appropriate guidance on how to minimize sleep disrupting exposures. Subjects will be provided external nasal dilator strips (Breathe Right®) and advised on how to maximize sleep time in a non-supine position using bed elevation, wedge pillows and/or objects affixed to the back of their night clothes as appropriate.

Sham PAP (Sham)

Intervention Type: DEVICE

In addition to receiving CMT, participants in this treatment arm will receive a sham PAP unit. Sham devices look like active PAP devices, however, the exhalation port is increased and an orifice-resistor is inserted between the pump and tubing, creating a marginal pressure. A heated humidifier will be provided with this device and PAP masks will be fit and provided following the same procedures as for the active-PAP arms.

Active PAP with RT Support (Active-Beh)

In addition to receiving CMT, participants will receive active-PAP. The treatment visit schedule is outlined below.

1. PAP Initial Set-Up

2. 1-week follow up (FU)

3. 1-month FU

4. 3-month FU

5. 6-month FU

6. 9-month FU (12-month follow-up protocol only)

All visits will take place with a PAP specialist. All follow-up visits will be anchored to the initial PAP set-up visit. At these visits, using the available data from the PAP monitor, the PAP specialist will discuss PAP use, mask leaks, and residual AHI to assist with troubleshooting. Adjustments to equipment would be performed as needed to improve adherence. Each follow-up visit with the PAP specialist will last 30 minutes.

Group Type: ACTIVE_COMPARATOR

Conservative Medical Therapy (CMT)

Intervention Type: BEHAVIORAL

All participants will meet with a research assistant who will provide 30 minutes of instruction on sleep hygiene and healthy lifestyle guidelines. Each subject's sleep routine will be reviewed with the aim to identify appropriate bed and wake times that provide a consistent schedule and allow for at least 7 hours of time in bed per night. Habits that may impact sleep, such as alcohol consumption, tobacco use, and exercise close to bedtime will be reviewed with appropriate guidance on how to minimize sleep disrupting exposures. Subjects will be provided external nasal dilator strips (Breathe Right®) and advised on how to maximize sleep time in a non-supine position using bed elevation, wedge pillows and/or objects affixed to the back of their night clothes as appropriate.

Active PAP with RT Support (Active-Beh)

Intervention Type: DEVICE

In addition to receiving CMT, participants will receive active-PAP and meet with a PAP-specialist . The CPAP specialist would meet with the participant in person throughout the course of the study (set-up, 1-week, 1-month, 3-month, 6-month, and 9-month). Using the available data from the PAP monitor, the PAP specialist will discuss PAP use, mask leaks, and residual AHI to assist with troubleshooting. Adjustments to equipment would be performed as needed to improve adherence. It is estimated that each in-person follow-up adherence visit with the PAP-specialist would last 30 minutes.

Active PAP with Behavioral Modification (Active+Beh)

In addition to receiving CMT and active-PAP, participants will have behavioral intervention sessions to promote PAP adherence. The treatment visit schedule is outlined below:

Visits with Behavioral Interventionist (in addition to active-PAP treatment visits):

1. PAP Initial Set-Up (in-person, 1-hr)

2. 1-week follow-up (FU) (in-person, 1-hr)

3. 1-month FU

4. 2-month FU

5. 3-month FU

6. 5-month FU

7. 8-month FU (12-month follow-up protocol only)

All follow-up visits will be anchored to the initial PAP set-up visit. PAP treatment visits will occur as outlined in the active-PAP arm.

All behavioral intervention visits will be 30-min phone calls, unless otherwise noted. The intervention will be based on social cognitive theory and feedback concerning adherence with targeted problem solving training.

Group Type: ACTIVE_COMPARATOR

Conservative Medical Therapy (CMT)

Intervention Type: BEHAVIORAL

All participants will meet with a research assistant who will provide 30 minutes of instruction on sleep hygiene and healthy lifestyle guidelines. Each subject's sleep routine will be reviewed with the aim to identify appropriate bed and wake times that provide a consistent schedule and allow for at least 7 hours of time in bed per night. Habits that may impact sleep, such as alcohol consumption, tobacco use, and exercise close to bedtime will be reviewed with appropriate guidance on how to minimize sleep disrupting exposures. Subjects will be provided external nasal dilator strips (Breathe Right®) and advised on how to maximize sleep time in a non-supine position using bed elevation, wedge pillows and/or objects affixed to the back of their night clothes as appropriate.

Active PAP with Behavioral Modification (Active+Beh)

Intervention Type: DEVICE

In addition to receiving CMT and active-PAP, participants will meet with a behavioral interventionist in addition to PAP-specialist visits. Participants also would speak with the behavioral interventionist over the course of the study (set up, 1-week, 3-week, 1-month, 2-months, 3-months, 5-months and 8-months). The duration of the first 2 behavioral intervention sessions are estimated to be 1-hour long, with subsequent 30-minutes intervention sessions. The intervention will be based on social cognitive theory and feedback concerning adherence with targeted problem solving training.

Interventions

Conservative Medical Therapy (CMT)

All participants will meet with a research assistant who will provide 30 minutes of instruction on sleep hygiene and healthy lifestyle guidelines. Each subject's sleep routine will be reviewed with the aim to identify appropriate bed and wake times that provide a consistent schedule and allow for at least 7 hours of time in bed per night. Habits that may impact sleep, such as alcohol consumption, tobacco use, and exercise close to bedtime will be reviewed with appropriate guidance on how to minimize sleep disrupting exposures. Subjects will be provided external nasal dilator strips (Breathe Right®) and advised on how to maximize sleep time in a non-supine position using bed elevation, wedge pillows and/or objects affixed to the back of their night clothes as appropriate.

Intervention Type: BEHAVIORAL

Sham PAP (Sham)

In addition to receiving CMT, participants in this treatment arm will receive a sham PAP unit. Sham devices look like active PAP devices, however, the exhalation port is increased and an orifice-resistor is inserted between the pump and tubing, creating a marginal pressure. A heated humidifier will be provided with this device and PAP masks will be fit and provided following the same procedures as for the active-PAP arms.

Intervention Type: DEVICE

Active PAP with RT Support (Active-Beh)

In addition to receiving CMT, participants will receive active-PAP and meet with a PAP-specialist . The CPAP specialist would meet with the participant in person throughout the course of the study (set-up, 1-week, 1-month, 3-month, 6-month, and 9-month). Using the available data from the PAP monitor, the PAP specialist will discuss PAP use, mask leaks, and residual AHI to assist with troubleshooting. Adjustments to equipment would be performed as needed to improve adherence. It is estimated that each in-person follow-up adherence visit with the PAP-specialist would last 30 minutes.

Intervention Type: DEVICE

Active PAP with Behavioral Modification (Active+Beh)

In addition to receiving CMT and active-PAP, participants will meet with a behavioral interventionist in addition to PAP-specialist visits. Participants also would speak with the behavioral interventionist over the course of the study (set up, 1-week, 3-week, 1-month, 2-months, 3-months, 5-months and 8-months). The duration of the first 2 behavioral intervention sessions are estimated to be 1-hour long, with subsequent 30-minutes intervention sessions. The intervention will be based on social cognitive theory and feedback concerning adherence with targeted problem solving training.

Intervention Type: DEVICE

Other Intervention Names

Breathe Right® external dilator strips; REMstar Pro M Series (Philips-Respironics); S9 (ResMed); REMstar Pro M Series (Philips-Respironics); S9 (ResMed); REMstar Pro M Series (Philips-Respironics); S9 (ResMed)

Eligibility Criteria

Inclusion Criteria

• Obstructive apnea hypopnea index (AHI) ≥ 15
• Age 45-75 years, or 55 to 75 yrs if without established Cardiovascular Disease (CVD)
• Ability to provide informed consent, with the patient and physician acknowledging accepting uncertainty on the role of PAP in CVD prevention.
• Established CVD,or having diabetes mellitus, defined by one or more of the following:

1. Prior myocardial infarction

2. Coronary artery revascularization procedure (≥4 months before study entry)

3. Angiographically documented stenosis (>70%) of a major coronary artery

4. Prior ischemic stroke without major functional impairment

5. Diabetes mellitus treated with medication or ≥ 2 fasting glucose levels ≥ 126 mg/dl

OR

Three or more of the following established CVD risk factors:

1. Hypertension treated with medications or systolic BP > 140 or diastolic BP > 90 on ≥ 2 occasions

2. Male sex

3. BMI ≥ 30

4. Total cholesterol > 240 mg/dl or LDL cholesterol > 160 mg/dl or HDL < 45 mg/dl

5. > 10 pack years of smoking

Exclusion Criteria

• Diagnosed heart failure with known cardiac ejection fraction of < 35% or New York Heart Association (NYHA) class 3 or 4 status
• Less than 4 months since myocardial infarction (MI), stroke or revascularization procedure
• Poorly controlled hypertension (>170/>100)
• Prior stroke with functional impairment interfering with ability to complete the protocol
• Severe uncontrolled medical problems or medications that may influence measurements or impair ability to participate in the study exams (e.g. oral steroids; chronic opioid use; self- reported chronic kidney disease or, if measured, creatinine > 2.5 mg/dl or glomerular filtration rate (GFR) < 30; anemia with Hgb < 10, etc.)
• Resting oxygen saturation < 90% or nocturnal oxygen saturation <85% for > 10% of the sleep period;
• Use of prescribed PAP for sleep apnea within the prior 2 years
• Report of inability to spend >6 hrs in bed
• Any use of prescribed PAP for sleep apnea
• Severe sleepiness defined by an Epworth Sleepiness Score of >14 or report of falling asleep driving in the prior 2 years
• Working as a professional driver
• Low risk related to having sleep apnea defined by a Berlin Score < 2
• Central sleep apnea, with >50% of respiratory events classified as central apneas
• Refusal to consider PAP use after an initial split-night PAP study (pre-randomization)
• Concurrent involvement in another research study that will result in a conflict as determined by study doctors

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Susan Redline

Professor and Senior Physician of Sleep Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Susan Redline, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Murray Mittleman, MD, DrPH

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

Zhao YY, Wang R, Gleason KJ, Lewis EF, Quan SF, Toth CM, Song Y, Morrical M, Rueschman M, Mittleman MA, Redline S. Effect of continuous positive airway pressure treatment on ambulatory blood pressures in high-risk sleep apnea patients: a randomized controlled trial. J Clin Sleep Med. 2022 Aug 1;18(8):1899-1907. doi: 10.5664/jcsm.10012.

Reference Type: DERIVED

PMID: 35459446 (View on PubMed)

Reid ML, Gleason KJ, Bakker JP, Wang R, Mittleman MA, Redline S. The role of sham continuous positive airway pressure as a placebo in controlled trials: Best Apnea Interventions for Research Trial. Sleep. 2019 Aug 1;42(8):zsz099. doi: 10.1093/sleep/zsz099.

Reference Type: DERIVED

PMID: 31116848 (View on PubMed)

Bakker JP, Wang R, Weng J, Aloia MS, Toth C, Morrical MG, Gleason KJ, Rueschman M, Dorsey C, Patel SR, Ware JH, Mittleman MA, Redline S. Motivational Enhancement for Increasing Adherence to CPAP: A Randomized Controlled Trial. Chest. 2016 Aug;150(2):337-45. doi: 10.1016/j.chest.2016.03.019. Epub 2016 Mar 24.

Reference Type: DERIVED

PMID: 27018174 (View on PubMed)

Yaggi HK, Mittleman MA, Bravata DM, Concato J, Ware J, Stoney CM, Redline S. Reducing cardiovascular risk through treatment of obstructive sleep apnea: 2 methodological approaches. Am Heart J. 2016 Feb;172:135-43. doi: 10.1016/j.ahj.2015.07.033. Epub 2015 Sep 11.

Reference Type: DERIVED

PMID: 26856225 (View on PubMed)

Other Identifiers

2010P002671

Identifier Type: -

Identifier Source: org_study_id