Sleep Apnea Intervention for Cardiovascular Disease Reduction

NCT01261390 | Completed Results DMC

• 1 other identifier: 2010P002671
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 1

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. 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:
2. 2.Active-Pap with respiratory therapist visits only
3. 3.Active-Pap with respiratory therapist visits and cognitive behavioral therapist visits.
4. 4.Alternative PAP Group (Sham): Will receive lower air delivery level than active-PAP therapy group. Will also have meetings with respiratory therapist.
5. 5.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.

Conditions

Obstructive Sleep Apnea

Keywords

Sleep Apnea; Heart Disease; Risk factors for heart disease

Outcome Measures

Primary Outcomes (7)

• Change From Baseline in 24-hour Blood Pressure at Months 6 and 12 by Pooled Arms

  Blood pressure data was collected using a 24-hour ambulatory blood pressure monitor. The 2 Active arms and 2 Control arms were pooled to create a 2-arm analysis. Outcome reported is mean of change from baseline to 6-months and baseline to 12-months. Control arms and Active arms were pooled, respectively, for analysis.

  Mean of 6- and 12-months

• Difference in CPAP Adherence by Active Treatment Arm

  Adherence to CPAP therapy was tracked remotely by modem transmission. Outcome reported is mean hours of PAP use per night at the 6-month timepoint. Comparison is between those with and without assignment to Motivational Enhancement as part of treatment randomization.

  6-months

• Change From Baseline in 24-hour Blood Pressure at Months 6 and 12 (4 Arms)

  Blood pressure data was collected using a 24-hour ambulatory blood pressure monitor. Average of changes from baseline to 6 months and from baseline to 12 months.

  Mean of 6- and 12-months

• Change From Baseline in 24-hour Blood Pressure at Month 12 by Pooled Arms

  Blood pressure data was collected using a 24-hour ambulatory blood pressure monitor. The 2 Active arms and 2 Control arms were pooled to create a 2-arm analysis. Outcome reported is change from baseline to 12-months. Control arms and Active arms were pooled, respectively, for analysis.

  12-months

• Change From Baseline in 24-hour Blood Pressure at Month 6 by Pooled Arms

  Blood pressure data was collected using a 24-hour ambulatory blood pressure monitor. The 2 Active arms and 2 Control arms were pooled to create a 2-arm analysis. Outcome reported mean change from baseline to 6-months. Control arms and Active arms were pooled, respectively, for analysis.

  6-months

• Change From Baseline in 24-hour Blood Pressure at Month 12 (4 Arms)

  Blood pressure data was collected using a 24-hour ambulatory blood pressure monitor. Outcome reported is mean change from baseline to 12-months.

  12-months

• Change From Baseline in 24-hour Blood Pressure at Month 6 (4 Arms)

  Blood pressure data was collected using a 24-hour ambulatory blood pressure monitor. Outcome reported is mean change from baseline to 6-months.

  6-months

Secondary Outcomes (34)

• Change in 36-Item Short Form Survey (SF-36) Measures (4 Arm)

  Mean of 6- and 12-months

• Change in Epworth Sleepiness Scale (ESS) (4 Arm)

  Mean of 6- and 12-months

• Change in Patient Health Questionnaire (PHQ8) (4 Arm)

  Mean of 6- and 12-months

• Change in the Calgary Sleep Apnea Quality of Life Index (SAQLI) (4 Arm)

  Mean of 6- and 12-months

• Change in C-Reactive Protein at Months 6 and 12 (4 Arm)

  Mean of 6- and 12-months

Study Arms (4)

Conservative Medical Therapy (CMT)

PLACEBO COMPARATOR

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.

Behavioral: Conservative Medical Therapy (CMT)

Sham PAP (Sham)

SHAM COMPARATOR

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.

Behavioral: Conservative Medical Therapy (CMT); Device: Sham PAP (Sham)

Active PAP with RT Support (Active-Beh)

ACTIVE COMPARATOR

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.

Behavioral: Conservative Medical Therapy (CMT); Device: Active PAP with RT Support (Active-Beh)

Active PAP with Behavioral Modification (Active+Beh)

ACTIVE COMPARATOR

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.

Behavioral: Conservative Medical Therapy (CMT); Device: Active PAP with Behavioral Modification (Active+Beh)

Interventions

Conservative Medical Therapy (CMT) 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.

Also known as: Breathe Right® external dilator strips

Active PAP with Behavioral Modification (Active+Beh); Active PAP with RT Support (Active-Beh); Conservative Medical Therapy (CMT); Sham PAP (Sham)

Sham PAP (Sham) 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.

Also known as: REMstar Pro M Series (Philips-Respironics), S9 (ResMed)

Sham PAP (Sham)

Active PAP with RT Support (Active-Beh) 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.

Also known as: REMstar Pro M Series (Philips-Respironics), S9 (ResMed)

Active PAP with RT Support (Active-Beh)

Active PAP with Behavioral Modification (Active+Beh) 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.

Also known as: REMstar Pro M Series (Philips-Respironics), S9 (ResMed)

Active PAP with Behavioral Modification (Active+Beh)

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Prior myocardial infarction
• Coronary artery revascularization procedure (≥4 months before study entry)
• Angiographically documented stenosis (\>70%) of a major coronary artery
• Prior ischemic stroke without major functional impairment
• Diabetes mellitus treated with medication or ≥ 2 fasting glucose levels ≥ 126 mg/dl
• Three or more of the following established CVD risk factors:
• Hypertension treated with medications or systolic BP \> 140 or diastolic BP \> 90 on ≥ 2 occasions
• Male sex
• BMI ≥ 30
• Total cholesterol \> 240 mg/dl or LDL cholesterol \> 160 mg/dl or HDL \< 45 mg/dl
• \> 10 pack years of smoking

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (4)

• 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.

  PMID: 35459446 DERIVED

• 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.

  PMID: 31116848 DERIVED

• 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.

  PMID: 27018174 DERIVED

• 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.

  PMID: 26856225 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Sleep Apnea Syndromes; Heart Diseases

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Susan Redline
• Organization: Brigham and Women's Hospital

sredline1@rics.bwh.harvard.edu

617-732-5859

Study Officials

• Susan Redline, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Murray Mittleman, MD, DrPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Senior Physician of Sleep Medicine

Study Record Dates

• First Submitted: December 15, 2010
• First Posted: December 16, 2010
• Study Start: March 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 30, 2017
• Results First Posted: May 30, 2017

Record last verified: 2017-04

Locations

US (1)