The Role of Obstructive Sleep Apnea in Children With Fatty Liver Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Changes in Hepatic Fat Content [baseline and 12 weeks]
Abdominal MRI to measure percent liver fat done at baseline and 12 weeks.
Secondary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale University | New Haven | Connecticut | United States | 06520 |
Sponsors and Collaborators
- Yale University
- American Heart Association
Investigators
- Principal Investigator: Nicola Santoro, MD, Yale University
Study Documents (Full-Text)
More Information
Publications
None provided.- 1404013732
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | C-pap Intervention |
|---|---|
| Arm/Group Description | Subjects who underwent measurement of the hepatic fat content before and after the C-pap |
| Period Title: Overall Study | |
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | C-pap Intervention |
|---|---|
| Arm/Group Description | Subjects undergoing measurements of hepatic fat content before and after C-pap |
| Overall Participants | 1 |
| Age (Count of Participants) | |
| <=18 years |
1
100%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
1
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
1
100%
|
| Not Hispanic or Latino |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
0
0%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
1
100%
|
| Region of Enrollment (Count of Participants) | |
| United States |
1
100%
|
Outcome Measures
| Title | Changes in Hepatic Fat Content |
|---|---|
| Description | Abdominal MRI to measure percent liver fat done at baseline and 12 weeks. |
| Time Frame | baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Presented is the change from baseline to 12 weeks in a single patient. |
| Arm/Group Title | C-pap Intervention |
|---|---|
| Arm/Group Description | Subjects who underwent the measure of hepatic fat content before and after the C-pap |
| Measure Participants | 1 |
| Number [percentage of hepatic liver fat] |
-4.8
|
| Title | Changes in Two Hour Glucose |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | C-pap Intervention |
|---|---|
| Arm/Group Description | Subjects who underwent the measure of hepatic fat content before and after the C-pap |
| Measure Participants | 1 |
| Number [mg/dl] |
5
|
Adverse Events
| Time Frame | 12 weeks | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | C-PAP Intervention | |
| Arm/Group Description | 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. 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. | |
All Cause Mortality |
||
| C-PAP Intervention | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | |
Serious Adverse Events |
||
| C-PAP Intervention | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| C-PAP Intervention | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Nicola Santoro |
|---|---|
| Organization | Yale University |
| Phone | 2037376356 |
| nicola.santoro@yale.edu |
- 1404013732