Obstructive Sleep Apnoea and CPAP Treatment Response in Patients With Non-alcoholic Fatty Liver Disease

• ClinicalTrials.gov Identifier: NCT02728765
• Recruitment Status: Completed
• First Posted: April 5, 2016
• Last Update Posted: May 7, 2019
• Sponsor: Chinese University of Hong Kong
• Information provided by (Responsible Party): Prof David Shu Cheong Hui, Chinese University of Hong Kong

Study Description

Brief Summary:

To study the frequency of obstructive sleep apnea (OSA) and continuous positive airway pressure (CPAP) treatment response in patients with non-alcoholic fatty liver disease (NAFLD).

It is hypothesized that CPAP treatment may improve the activities of NAFLD in those with concomitant OSA.

A screening study for OSA followed by a randomized controlled trial of patients with biopsy proven NAFLD being followed up at the hepatology clinic.

Home sleep study, Epworth sleepiness score (ESS), paired proton magnetic resonance spectroscopy (MRS), transient elastography by fibroscan, serum cytokeratin-18 fragment, liver function tests and liver biopsy (only for those with fibroscan evidence of advanced liver fibrosis).

Patients with confirmed symptomatic OSA will be randomized to receive auto CPAP or subtherapeutic CPAP as control over 6 months.

Primary outcome: changes in intrahepatic triglyceride content (IHTG) measured by proton-MRS after 6 months of auto CPAP versus subtherapeutic CPAP.

Condition or disease	Intervention/treatment	Phase
Obstructive Sleep Apnea; Non-alcoholic Fatty Liver Disease	Device: Continuous positive airway pressure (CPAP)	Not Applicable

Detailed Description:

Investigators propose to screen for obstructive sleep apnea (OSA) by performing a home sleep study on all the patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) being followed up at the Hepatology Clinic, Prince of Wales Hospital, Hong Kong, in phase one of this study. The following conditions have already been excluded as the underlying cause of liver disease in this specific NAFLD cohort: history of excessive alcoholic consumption (more than 30 g/day for men and 20 g/day for women), secondary causes of hepatic steatosis (such as chronic use of systemic corticosteroids), positive hepatitis B surface antigen, anti-hepatitis C virus antibody, or histological evidence of other concomitant chronic liver diseases.

OSA syndrome is defined by apnoea-hypopnoea index (AHI) of 5 per hours or more of sleep plus excessive daytime sleepiness or two of the following symptoms: choking or gasping during sleep, recurrent awakenings from sleep, unrefreshed sleep, daytime fatigue, and impaired concentration. All patients with suspected OSA will undergo initial assessment at the respiratory clinic with the Epworth sleepiness score (ESS) and symptoms evaluation. Patients who have ESS score >9 or at least two OSA symptoms as described above will be invited to join phase two of the study. They will be invited to undergo a home sleep study.

Those with biopsy proven NAFLD who have AHI≥ 5/hr will be randomized into either group A ) auto CPAP with range 4-12 cmH20 or group B) Subtherapeutic CPAP with the auto CPAP fixed at 4 cmH20 by a balanced block design by a third party not involved in the trial.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Obstructive Sleep Apnoea and CPAP Treatment Response in Patients With Non-alcoholic Fatty Liver Disease
• Actual Study Start Date: July 5, 2016
• Actual Primary Completion Date: March 30, 2019
• Actual Study Completion Date: March 30, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: auto CPAP; Each patient will be interviewed by the physician on duty and invited to participate in the overnight hospital based auto continuous positive airway pressure (CPAP) titration study for 1 night and then commencement of auto CPAP treatment for 6 months.	Device: Continuous positive airway pressure (CPAP); Continuous positive airway pressure (CPAP) is the gold standard treatment for patients with obstructive sleep apnea (OSA). In a previous trials comparing therapeutic CPAP vs subtherapeutic CPAP, CPAP could reduce 24-hour mean blood pressure in mildly sleepy patients with OSA over 3 months whereas our one-year prospective study has shown that reduction of carotid artery intima-media thickness of OSA patients occurred mostly in the first 6 months and was sustained at 12 months in patients with CPAP compliance about 4.7 hours per night.
Placebo Comparator: Subtherapeutic CPAP; Following detection of obstructive sleep apnea (OSA), each patient randomized to this arm will receive the same CPAP education, mask fitting and short auto CPAP trial for acclimatization but their auto CPAP device will be set at a subtherapeutic level of 4 cmH20 for use at home. The patients randomized to both arms will receive the same general education about OSA, sleep hygiene, avoidance of alcohol, and weight reduction if appropriate.	Device: Continuous positive airway pressure (CPAP); Continuous positive airway pressure (CPAP) is the gold standard treatment for patients with obstructive sleep apnea (OSA). In a previous trials comparing therapeutic CPAP vs subtherapeutic CPAP, CPAP could reduce 24-hour mean blood pressure in mildly sleepy patients with OSA over 3 months whereas our one-year prospective study has shown that reduction of carotid artery intima-media thickness of OSA patients occurred mostly in the first 6 months and was sustained at 12 months in patients with CPAP compliance about 4.7 hours per night.

Outcome Measures

Primary Outcome Measures :

1. Changes in intrahepatic triglyceride content (IHTG) [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. Changes in Epworth Sleepiness Score [ Time Frame: 6 months ]
2. Transient elastography by fibroscan [ Time Frame: 6 months ]
3. Serum cytokeratin-18 fragment [ Time Frame: 6 months ]
4. Change in non-alcoholic fatty liver disease(NAFLD) activity score [ Time Frame: 6 months ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• symptoms of obstructive sleep apnea with home sleep study showing apnea hypopnea index of 5/hour or more, subjects with non-alcoholic fatty liver disease (NAFLD) diagnosed by liver biopsy.

Exclusion Criteria:

• (a) unstable cardiovascular diseases (e.g. recent unstable angina, myocardial infarction, stroke or transient ischemic attack within the previous 6 months or severe left ventricular failure), (b) neuromuscular disease affecting or potentially affecting respiratory muscles,(c) moderate to severe respiratory disease (i.e. breathlessness affecting activities of daily living) or documented hypoxemia or awake oxygen saturation <92% or (d) psychiatric disease that limits the ability to give informed consent or complete the study, (e) professional drivers, (f) gross structural ear-nose-throat abnormalities (large nasal polyps, gross nasal turbinate hypertrophy or septal deviation and enlarged "kissing" tonsils of significant size) who need early intervention.

Contacts and Locations

Locations

Hong Kong

Prince of Wales Hospital

Hong Kong, Hong Kong

Sponsors and Collaborators

Chinese University of Hong Kong

Investigators

• Principal Investigator: David SC Hui, MD; Chinese University of Hong Kong

More Information

• Responsible Party: Prof David Shu Cheong Hui, Professor, Chinese University of Hong Kong
• ClinicalTrials.gov Identifier: NCT02728765
• Other Study ID Numbers: Fatty liver/OSA/2016
• First Posted: April 5, 2016
• Last Update Posted: May 7, 2019
• Last Verified: May 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Digestive System Diseases