Non Alcoholic Fatty Liver Disease
Conditions
Keywords
non alcoholic fatty liver, childhood obesity, Sleep Apnea
Brief summary
The purpose of this study is to examine whether CPAP therapy can reduce or eliminate hepatic fat accumulation in obese children and adolescents.
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.
Interventions
DEVICEContinuous 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.
Sponsors
American Heart Association
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
9 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Hepatic Fat Content | baseline and 12 weeks | Abdominal MRI to measure percent liver fat done at baseline and 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Two Hour Glucose | baseline and 12 weeks | 2 hour glucose measured by an oral glucose tolerance test done at baseline and 12 weeks. Data are presented as mg/dl. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| C-pap Intervention Subjects undergoing measurements of hepatic fat content before and after C-pap | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | C-pap Intervention |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 1 Participants |
| Sex: Female, Male Gender Female | 0 Participants |
| Sex: Female, Male Gender Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Changes in Hepatic Fat Content
Abdominal MRI to measure percent liver fat done at baseline and 12 weeks.
Time frame: baseline and 12 weeks
Population: Presented is the change from baseline to 12 weeks in a single patient.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C-pap Intervention | Changes in Hepatic Fat Content | -4.8 percentage of hepatic liver fat |
Secondary
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.
Time frame: baseline and 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C-pap Intervention | Changes in Two Hour Glucose | 5 mg/dl |