Trial Outcomes & Findings for The Sleep, Liver Evaluation and Effective Pressure Study (NCT NCT01482065)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

6 months

Results posted on

2017-01-04

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Deferred CPAP 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.	CPAP 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 Study STARTED	4	5
Overall Study COMPLETED	4	4
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Deferred CPAP 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.	CPAP 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 Study Withdrawal by Subject	0	1

Baseline Characteristics

The Sleep, Liver Evaluation and Effective Pressure Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Deferred CPAP n=4 Participants 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.	CPAP n=5 Participants 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 n=9 Participants Total of all reporting groups
Age, Continuous	58 years STANDARD_DEVIATION 3.74 • n=5 Participants	42.8 years STANDARD_DEVIATION 16.63 • n=7 Participants	49.56 years STANDARD_DEVIATION 14.73 • n=5 Participants
Gender Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Gender Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: We were unable to obtain liver biopsy on most of our participants due to limited clinical indications.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 Months

Population: Withdrawal by subject in CPAP group.

Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) activity.

Outcome measures

Outcome measures
Measure	Deferred CPAP n=4 Participants 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.	CPAP n=5 Participants 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.
Liver Values ALT Baseline	37.25 U/L Standard Deviation 20.66	53.8 U/L Standard Deviation 27.26
Liver Values ALT 6 Months	29 U/L Standard Deviation 7.84	40.5 U/L Standard Deviation 10.36
Liver Values AST Baseline	26.75 U/L Standard Deviation 9.44	32.6 U/L Standard Deviation 19.77
Liver Values AST 6 Months	23.5 U/L Standard Deviation 7.83	29.75 U/L Standard Deviation 21.29

SECONDARY outcome

Timeframe: 6 months

Population: 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).

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 Months

Population: 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.

Outcome measures

Outcome measures
Measure	Deferred CPAP n=4 Participants 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.	CPAP n=5 Participants 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.
MRI Indices MRI Baseline	10.57 percentage of fat in liver Standard Deviation 6.33	15.406 percentage of fat in liver Standard Deviation 3.77
MRI Indices MRI 6 Months	8.69 percentage of fat in liver Standard Deviation 4.82	18.76 percentage of fat in liver Standard Deviation 11.72

Adverse Events

Deferred CPAP

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

CPAP

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Seva Polotsky, M.D., PhD

Johns Hopkins University

Phone: 410-550-6386

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place