Liver and Fat Regulation in Overweight Adolescent Girls

Phase 2

Completed

• Conditions: Obesity; Polycystic Ovarian Syndrome; Hepatic Steatosis
• Interventions: Drug: Byetta 5Mcg Pen Injection

• Registration Number: NCT02157974
• Lead Sponsor: University of Colorado, Denver

Brief 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.

Detailed 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).

Study Timeline

• Study First Submitted: 2014-06-04
• Study First Submitted QC: 2014-06-04
• Study First Posted: 2014-06-06
• Study Start: 2014-08
• Primary Completion: 2022-12
• Study Completion: 2022-12
• Results First Submitted: 2024-04-15
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-31
• Last Update Submitted: 2024-05-31
• Results First Posted: 2024-06-04
• Last Update Posted: 2024-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 92

Inclusion Criteria

• Females
• 2 years post-menarche
• BMI percentile >90%

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PCOS, medication naive + Byetta	Byetta 5Mcg Pen Injection	PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta.

Primary Outcome Measures

Name	Time	Method
Hepatic Glucose Release	Measured up to 4 months from enrollment	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

Secondary Outcome Measures

Name	Time	Method
Hepatic de Novo Lipogenesis	Measured up to 4 months from enrollment	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.
Hepatic Fat Fraction	Measured up to 4 months from enrollment	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.
Hepatic Phosphate Concentrations	Measured up to 4 months from enrollment	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)
Rates of Lipolysis	Measured up to 4 months from enrollment	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.

Trial Locations

Locations (1)

University of Colorado Anshutz Medical Campus/Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States