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The Sleep, Liver Evaluation and Effective Pressure Study (SLEEP)

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ClinicalTrials.gov Identifier: NCT01482065
Recruitment Status : Completed
First Posted : November 30, 2011
Results First Posted : January 4, 2017
Last Update Posted : January 4, 2017
Sponsor:
Collaborator:
ResMed Foundation
Information provided by (Responsible Party):
Johns Hopkins University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Non Alcoholic Fatty Liver Disease
Obstructive Sleep Apnea
Intervention Device: CPAP (ResMed S9 autoset CPAP)
Enrollment 40
Recruitment Details  
Pre-assignment Details 212 subjects screened; 166 subjects were excluded. 40 were included. 39 started in the protocol. 8 patients dropped out. Liver MRI completed in 27 subjects. 12 patients were excluded after liver MRI; 14 subjects had sleep studies. 5 patients did not proceed to the CPAP trial. 9 patients were randomized.
Arm/Group Title Deferred CPAP CPAP
Hide Arm/Group Description

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the deferred CPAP group will sign a consent to agree to defer CPAP use for 4 months to complete the study.

Criteria for Obstructive Sleep Apnea (OSA) severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

CPAP (ResMed S9 autoset CPAP): A ResMed S9 autoset CPAP device will be utilized throughout the study.

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the CPAP group will be sent home with an autoset CPAP device, which they will be instructed to utilize for 4 months. The CPAP device will be set in the "auto mode" so that it will automatically adjust the pressure at night to eliminate upper airway obstruction during sleep.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

Period Title: Overall Study
Started 4 5
Completed 4 4
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Arm/Group Title Deferred CPAP CPAP Total
Hide Arm/Group Description

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the deferred CPAP group will sign a consent to agree to defer CPAP use for 4 months to complete the study.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

CPAP (ResMed S9 autoset CPAP): A ResMed S9 autoset CPAP device will be utilized throughout the study.

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the CPAP group will be sent home with an autoset CPAP device, which they will be instructed to utilize for 4 months. The CPAP device will be set in the "auto mode" so that it will automatically adjust the pressure at night to eliminate upper airway obstruction during sleep.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

Total of all reporting groups
Overall Number of Baseline Participants 4 5 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 5 participants 9 participants
58  (3.74) 42.8  (16.63) 49.56  (14.73)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 5 participants 9 participants
Female
2
  50.0%
2
  40.0%
4
  44.4%
Male
2
  50.0%
3
  60.0%
5
  55.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 5 participants 9 participants
4 5 9
1.Primary Outcome
Title Cross Sectional Analysis of NAFLD Versus Sleep Apnea Severity Indices (AHI)
Hide Description Cross-sectional analysis will be performed in NAFLD study participants from the Johns Hopkins (JH) Hepatology Clinic to examine the relationship between findings on liver biopsy and sleep apnea severity indices. The main predictor variable will be presence/severity of OSA and nocturnal oxyhemoglobin desaturation (assessed by T90%, time w/ oxyhemoglobin desaturation < 90%; Delta SaO2 between baseline and minimal oxyhemoglobin saturation, and standard deviation of nocturnal SaO2). Our primary outcome will be NAFLD activity score on biopsy.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
We were unable to obtain liver biopsy on most of our participants due to limited clinical indications.
Arm/Group Title Deferred CPAP CPAP
Hide Arm/Group Description:

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the deferred CPAP group will sign a consent to agree to defer CPAP use for 4 months to complete the study.

Criteria for Obstructive Sleep Apnea (OSA) severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

CPAP (ResMed S9 autoset CPAP): A ResMed S9 autoset CPAP device will be utilized throughout the study.

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the CPAP group will be sent home with an autoset CPAP device, which they will be instructed to utilize for 4 months. The CPAP device will be set in the "auto mode" so that it will automatically adjust the pressure at night to eliminate upper airway obstruction during sleep.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Liver Values
Hide Description Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) activity.
Time Frame 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Withdrawal by subject in CPAP group.
Arm/Group Title Deferred CPAP CPAP
Hide Arm/Group Description:

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the deferred CPAP group will sign a consent to agree to defer CPAP use for 4 months to complete the study.

Criteria for Obstructive Sleep Apnea (OSA) severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

CPAP (ResMed S9 autoset CPAP): A ResMed S9 autoset CPAP device will be utilized throughout the study.

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the CPAP group will be sent home with an autoset CPAP device, which they will be instructed to utilize for 4 months. The CPAP device will be set in the "auto mode" so that it will automatically adjust the pressure at night to eliminate upper airway obstruction during sleep.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

Overall Number of Participants Analyzed 4 5
Mean (Standard Deviation)
Unit of Measure: U/L
ALT Baseline Number Analyzed 4 participants 5 participants
37.25  (20.66) 53.8  (27.26)
ALT 6 Months Number Analyzed 4 participants 4 participants
29  (7.84) 40.5  (10.36)
AST Baseline Number Analyzed 4 participants 5 participants
26.75  (9.44) 32.6  (19.77)
AST 6 Months Number Analyzed 4 participants 4 participants
23.5  (7.83) 29.75  (21.29)
3.Secondary Outcome
Title Analysis of Variance (ANOVA) in CPAP Versus No-CPAP Therapy on NAFLD
Hide Description we will test our hypothesis that CPAP therapy improves NAFLD. The main independent variables will be CPAP vs. deferred-CPAP therapy. In a subanalysis, responses in the CPAP treatment group will be compared based on compliance. Compliance with CPAP is defined as using it on > 70% of the days, at least 4 h per night. Our primary outcome will be serum activity of ALT and AST. We will use ANOVA to examine changes in ALT and AST depending on CPAP therapy group and compliance. Secondary outcomes will include the degree of hepatic steatosis and fibrosis, as assessed by MRI.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
We were unable to achieve enrollment goals due to limited clinical indications. Thereby not obtaining enough participant data to do an Analysis of Variance (ANOVA).
Arm/Group Title Deferred CPAP CPAP
Hide Arm/Group Description:

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the deferred CPAP group will sign a consent to agree to defer CPAP use for 4 months to complete the study.

Criteria for Obstructive Sleep Apnea (OSA) severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

CPAP (ResMed S9 autoset CPAP): A ResMed S9 autoset CPAP device will be utilized throughout the study.

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the CPAP group will be sent home with an autoset CPAP device, which they will be instructed to utilize for 4 months. The CPAP device will be set in the "auto mode" so that it will automatically adjust the pressure at night to eliminate upper airway obstruction during sleep.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title MRI Indices
Hide Description [Not Specified]
Time Frame 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
We were not able to obtain MRI data from 2 people within the CPAP group at 6 months. One withdrew from study and the other a clear scan could not be obtained.
Arm/Group Title Deferred CPAP CPAP
Hide Arm/Group Description:

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the deferred CPAP group will sign a consent to agree to defer CPAP use for 4 months to complete the study.

Criteria for Obstructive Sleep Apnea (OSA) severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

CPAP (ResMed S9 autoset CPAP): A ResMed S9 autoset CPAP device will be utilized throughout the study.

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the CPAP group will be sent home with an autoset CPAP device, which they will be instructed to utilize for 4 months. The CPAP device will be set in the "auto mode" so that it will automatically adjust the pressure at night to eliminate upper airway obstruction during sleep.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

Overall Number of Participants Analyzed 4 5
Mean (Standard Deviation)
Unit of Measure: percentage of fat in liver
MRI Baseline Number Analyzed 4 participants 5 participants
10.57  (6.33) 15.406  (3.77)
MRI 6 Months Number Analyzed 4 participants 3 participants
8.69  (4.82) 18.76  (11.72)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Deferred CPAP CPAP
Hide Arm/Group Description

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the deferred CPAP group will sign a consent to agree to defer CPAP use for 4 months to complete the study.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

CPAP (ResMed S9 autoset CPAP): A ResMed S9 autoset CPAP device will be utilized throughout the study.

Patients with moderate to severe apnea will be randomized to CPAP or deferred CPAP. Those in the CPAP group will be sent home with an autoset CPAP device, which they will be instructed to utilize for 4 months. The CPAP device will be set in the "auto mode" so that it will automatically adjust the pressure at night to eliminate upper airway obstruction during sleep.

Criteria for OSA severity are specifically designed to target patients with nocturnal hypoxemia, which is hypothesized to contribute to NAFLD progression. According to the guidelines of the American Academy of Sleep Medicine, apnea will be defined as cessation of airflow for ≥ 10 sec. and hypopnea will be defined as decreased airflow for ≥ 10 sec. leading to oxyhemoglobin desaturation ≥ 4%. Mild, moderate and severe OSA will be diagnosed by an AHI of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

All-Cause Mortality
Deferred CPAP CPAP
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Deferred CPAP CPAP
Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/5 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Deferred CPAP CPAP
Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)   0/5 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Seva Polotsky, M.D., PhD
Organization: Johns Hopkins University
Phone: 410-550-6386
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01482065     History of Changes
Other Study ID Numbers: NA_00048965
111481 ( Other Grant/Funding Number: ResMed Foundation )
First Submitted: November 15, 2011
First Posted: November 30, 2011
Results First Submitted: November 1, 2016
Results First Posted: January 4, 2017
Last Update Posted: January 4, 2017