The Sleep, Liver Evaluation and Effective Pressure Study

NCT01482065 | Completed Phase 2 Results DMC

• 2 other identifiers: NA_00048965111481
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to examine: 1) how common obstructive sleep apnea (OSA) is in patients with non-alcoholic fatty liver disease (NAFLD), 2) whether the severity of OSA is related to the severity of NAFLD, and 3) whether treatment of OSA with continuous positive airway pressure (CPAP) improved NAFLD progression. OSA is a condition caused by repetitive collapse of throat tissue during sleep that leads to falls in oxygen level and sleep disruption. OSA can be caused by obesity, and especially by fat found in the neck and belly. NAFLD is a common disease linked to obesity. NAFLD is part of a disease spectrum, which can progress from steatosis (fatty liver) to nonalcoholic steatohepatitis (NASH), a progressive fibrotic disease, in which cirrhosis and liver-related death can occur. Recent evidence in patients with obstructive sleep apnea (OSA) indicates that OSA is associated with NASH. How common OSA is in patients with biopsy-confirmed NAFLD and the effect of OSA treatment with CPAP on NASH is unknown.

Conditions

Non Alcoholic Fatty Liver Disease; Obstructive Sleep Apnea

Keywords

Non Alcoholic Fatty Liver Disease; NAFLD; Continuous Positive Airway Pressure; CPAP; CPAP Therapy; Apnea Hypopnea Index; Non alcoholic steatohepatitis; NASH; OSA; Obstructive Sleep Apnea; AHI

Outcome Measures

Primary Outcomes (1)

• Cross Sectional Analysis of NAFLD Versus Sleep Apnea Severity Indices (AHI)

  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.

  6 months

Secondary Outcomes (3)

• Liver Values

  6 Months

• Analysis of Variance (ANOVA) in CPAP Versus No-CPAP Therapy on NAFLD

  6 months

• MRI Indices

  6 Months

Study Arms (1)

CPAP

EXPERIMENTAL

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 Apnea-Hypopnea Index (AHI) of 5-14.9, 15-29.9, and ≥ 30 events/hr, respectively.

Device: CPAP (ResMed S9 autoset CPAP)

Interventions

CPAP (ResMed S9 autoset CPAP) DEVICE

A ResMed S9 autoset CPAP device will be utilized throughout the study. Throughout the study intervention period, subjects (for AHI\> 15) will be instructed to utilize their CPAP and adherence will be monitored using an automatic meter that is built into the CPAP device.

Also known as: ResMed S9 autoset CPAP

CPAP

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 21
• Diagnosis of NAFLD and BMI ≥ 30 or obesity with BMI \> 35 and \< 400lbs
• No other cause of liver disease other than NAFLD (as assessed by patient and physician surveys detailed below, blood work and magnetic resonance imaging(MRI))

You may not qualify if:

• Patients with sickle cell anemia, hemoglobinopathies and other hemolytic anemias
• Known clinical hypersensitivity or a history of asthma or allergic respiratory disorders
• Advanced renal failure (currently requiring dialysis or with a Glomerular Filtration rate \< 30cc/min)
• Pregnancy
• History of CPAP treatment for OSA
• Recent weight loss (6 months) ≥ 10%
• Current alcohol use \> 20 g/day in women and \> 30 g/day in men, or prior use for ≥ 3 consecutive months during the previous 5 years as assessed with the Lifetime Drinking History Questionnaire Viral hepatitis A, B and C
• Autoimmune hepatitis
• Hemochromatosis
• Wilson's disease
• Alpha-1-antitrypsin deficiency
• Primary sclerosing cholangitis
• Cirrhosis of any etiology
• History of HIV infection and/or HAART therapy
• Evidence of drug-induced liver injury

Sponsors & Collaborators

• Johns Hopkins University: lead
• ResMed Foundation: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Sleep Apnea, Obstructive

Interventions

Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Results Point of Contact

• Title: Dr. Seva Polotsky, M.D., PhD
• Organization: Johns Hopkins University

vpolots1@jhmi.edu

410-550-6386

Study Officials

• Alan R Schwartz, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: November 30, 2011
• Study Start: November 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: October 1, 2015
• Last Updated: January 4, 2017
• Results First Posted: January 4, 2017

Record last verified: 2016-11

Locations

US (1)