The Role of Obstructive Sleep Apnea in Children With Fatty Liver Disease

The Role of Obstructive Sleep Apnea in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents

The purpose of this study is to examine whether CPAP therapy can reduce or eliminate hepatic fat accumulation in obese children and adolescents.

Study Overview

• Status: Terminated
• Conditions: Non Alcoholic Fatty Liver Disease
• Intervention / Treatment: Device: Continuous positive airway pressure (CPAP).

Detailed Description

NAFLD is emerging as one of the most common complications of childhood obesity. It is associated with and predicts the metabolic syndrome, independent of overall obesity. Recently, studies in obese adolescents have demonstrated that increased ALT levels are associated with deterioration in insulin sensitivity and glucose tolerance, as well as with increasing FFA and triglyceride levels. Further studies showed that the prevalence of metabolic syndrome and prediabetes increases with the increases in hepatic fat content in a cohort of obese adolescents. Moreover, the investigators found that the fatty liver is associated with a pronounced dyslipidemic profile characterized by large VLDL, small dense LDL, and decreased large HDL concentrations. Fatty liver, independent of visceral and intramyocellular lipid content plays a central role in the impairment of liver, muscle and adipose insulin sensitivity in obese adolescents. Thus, fatty liver disease may be the hepatic component of the metabolic syndrome. The synthesis of triglycerides in the liver is nutritionally regulated, and its formation from simple carbohydrates requires multiple metabolic pathways, including glycolysis and pyruvate oxidation to generate acetyl-CoA for fatty acid synthesis, NADPH generation to supply the reductive power, packaging of fatty acids into a glycerophosphate backbone, and finally, lipoprotein packaging to export triglycerides. Recent studies have shown an association between fatty liver and obstructive sleep apnea (OSA), a condition that has been estimated to affect up to 27% of obese children. In particular, OSA has been associated with the ALT levels and with the degree of steatohepatitis. Despite those evidences and the importance of NAFLD in the development of metabolic diseases, the information concerning the association between fatty liver and OSA in obese children and adolescents is quite sparse and in particular is unclear whether OSA itself can cause NAFLD or the two conditions just coexist as obesity complications. In this study the investigators will test the hypothesis that OSA is one of the determinants of hepatic fat accumulation. To prove the investigators hypothesis the investigators will select a group of individuals with NAFLD and OSA, who will undergo a weight maintenance diet and Continuous Positive Airway Pressure (CPAP) for 12 weeks. CPAP is FDA approved and represents the leading therapy for obstructive sleep apnea in children over age 7 and 40 lbs. To evaluate the effect of the CPAP on the intra hepatic fat accumulation the investigators will evaluate hepatic fat content with MRI at baseline and after the intervention.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sleep Apnea as diagnosed by clinical sleep study (Apnea Hypopnea index greater than 1)
• Evidence of NAFLD as diagnosed by screening MRI (hepatic fat fraction ≥5.5%) Obese child/adolescent between 9-21 years old
• Compliance with using C-pap as instructed

Exclusion Criteria:

• Medications or know disease known to alter glucose or insulin metabolism such as oral steroids, or certain psychiatric medications, such as Xeleca, Lithium and Paxil.
• Type 2 Diabetes Mellitus
• Medications for chronic anti-inflammatory effects
• Consumption of alcohol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C-PAP intervention; Continuous positive airway pressure is a commonly prescribed therapy for obstructive sleep apnea which is recommended for the treatment of obstructive sleep apnea in children and adults.	Device: Continuous positive airway pressure (CPAP).; Continuous positive airway pressure is a commonly prescribed therapy for obstructive sleep apnea which is recommended for the treatment of obstructive sleep apnea in children and adults.; Other Names: c-pap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Hepatic Fat Content	Abdominal MRI to measure percent liver fat done at baseline and 12 weeks.	baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Two Hour Glucose	2 hour glucose measured by an oral glucose tolerance test done at baseline and 12 weeks. Data are presented as mg/dl.	baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Nicola Santoro, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: May 7, 2014
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (Estimate): May 9, 2014

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: June 5, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Sleep Apnea; childhood obesity; non alcoholic fatty liver
• Additional Relevant MeSH Terms: Digestive System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Liver Diseases; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 1404013732

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No