Liver and Fat Regulation in Overweight Adolescent Girls

Obesity Clinical Trial

— APPLE  

Official title:

Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02157974
• Other study ID #: 14-0542
• Secondary ID: UL1TR001082K23DK
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 2014
• Est. completion date: December 2022

Study information

• Verified date: May 2024
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Women with polycystic ovarian syndrome (PCOS) have increased rates of hepatic steatosis compared to weight similar women with regular menses. It is unclear if this is related to high testosterone or insulin resistance. The investigators will assess hepatic glucose release, rates of lipolysis and hepatic de novo lipogenesis in the fasted and postprandial state to determine if alterations in the processes contribute to hepatic steatosis. Participants will be overweight, sedentary girls with or without PCOS. Those with PCOS will either be medication naive, or must be taking metformin or combined oral contraceptives (COCPs) for a period of at least 6 months prior to study procedures.

Description:

Hepatic glucose release will be assessed with a stable isotope glycerol tracer, lipolysis with a glycerol tracer, and hepatic de novo lipogenesis with an acetate tracer. Data will be collected fasting and after a glucose challenge. The degree of hepatic steatosis and abdominal fat partitioning will be assessed with Magnetic Resonance Imaging (MRI), and total body composition with Dual-energy X-ray absorptiometry (DEXA).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 12 Years to 21 Years

Eligibility

Inclusion Criteria:

• Females

• 2 years post-menarche

• BMI percentile >90%

Exclusion Criteria:

• Type 2 diabetes

• Anemia

• Liver disease

• Medications known to effect insulin sensitivity

• Cause of oligomenorrhea or hirsutism other than PCOS,

• >3 hours a week of moderate exercise.

Related Conditions & MeSH terms

• Fatty Liver
• Hepatic Steatosis
• Obesity
• Overweight
• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome

Intervention

Drug:
• Byetta 5Mcg Pen Injection
10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola

Locations

Country	Name	City	State
United States	University of Colorado Anshutz Medical Campus/Children's Hospital Colorado	Aurora	Colorado

Sponsors (3)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Center for Advancing Translational Sciences (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Whole Body Insulin Sensitivity	Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model using SAMM II software. This software uses participant weight, glucose and insulin concentrations at various time points during the oral glucose tolerance test to calculate the participant insulin sensitivity. The higher the Si value means more insulin sensitivity.	Measured up to 4 months from enrollment
Other	Sleep Quality	Apnea Hypopnea Index (AHI) will be measured using WatchPAT. In children and adolescents the scale that will be used is AHI>5 is considered mild sleep apnea. The higher the AHI, indicates more severe sleep apnea.; The AHI is the number of times you have apnea or hypopnea during one night, divided by the hours of sleep.; Normal sleep: An AHI of fewer than five events, on average, per hour Mild sleep apnea: An AHI of five to 14 events per hour Moderate sleep apnea: An AHI of 15 to 29 events per hour Severe sleep apnea: An AHI of 30 or more events per hour	Measured up to 4 months from enrollment
Other	Sleep Duration	Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data.	Measured up to 4 months from enrollment
Primary	Hepatic Glucose Release	Hepatic glucose release will be measured by the rate of appearance of a glucose tracer. Glucose rate of appearance reflects the amount of glucose being release by primarily the liver during fasting. A higher glucose rate of appearance is often seen with dysglycemia	Measured up to 4 months from enrollment
Secondary	Hepatic Phosphate Concentrations	Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy. The ratio of the following will be reported over total phosphate concentration: Phosphodiesterase (PDE), phosphomonoester (PME), Adenosine triphosphate (ATP), Inorganic Phosphate (Pi),Nicotinamide adenine dinucleotide phosphate (NADPH), Uridine diphosphate glucose (UDPG)	Measured up to 4 months from enrollment
Secondary	Rates of Lipolysis	Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer. Glycerol rate of appearance reflects the amount of glycerol being released into the blood stream as a results of lipolysis. Higher rates of lipolysis are thought to be associated with insulin resistance.	Measured up to 4 months from enrollment
Secondary	Hepatic Fat Fraction	Amount of fat in the liver measured by MRI and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver.	Measured up to 4 months from enrollment
Secondary	Hepatic de Novo Lipogenesis	Hepatic de novo lipogenesis will be measured by with an acetate tracer by mass spectroscopy. De novo lipogenesis can contribute to non-alcoholic fatty liver disease, so having a lower value is better.	Measured up to 4 months from enrollment