Liver and Fat Regulation in Overweight Adolescent Girls (APPLE)

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Obesity; Hepatic Steatosis; Polycystic Ovarian Syndrome

Treatments: Drug: Byetta 5Mcg Pen Injection

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02157974

14-0542

K23DK107871 (U.S. NIH Grant/Contract)

UL1TR001082 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 92 patients

Sex: Female

Ages: 12 to 21 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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92 participants in 5 patient groups

PCOS, medication naive + Byetta

Experimental group

Description:

PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta.

Treatment:

Drug: Byetta 5Mcg Pen Injection

Control

No Intervention group

Description:

Up to 25 girls without PCOS

PCOS medication naive

No Intervention group

Description:

Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.

PCOS on COCPs

No Intervention group

Description:

Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.

PCOS on metformin

No Intervention group

Description:

Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures