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Completed

NCT Number: NCT02157974

Liver and Fat Regulation in Overweight Adolescent Girls

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.

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Key information

Conditions

Hepatic Steatosis Adnexal Diseases Body Weight Cysts Digestive System Diseases Endocrine System Diseases Fatty Liver Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Gonadal Disorders Liver Diseases Neoplasms Nutrition Disorders Nutritional and Metabolic Diseases Obesity Ovarian Cysts Ovarian Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Polycystic Ovarian Syndrome Polycystic Ovary Syndrome Signs and Symptoms Urogenital Diseases

Age range

12 year–21 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

University of Colorado Anshutz Medical Campus/Children's Hospital Colorado

Aurora, Colorado, 80045, United States

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Byetta 5Mcg Pen Injection

Drug

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

Other names: Exenatide

Primary outcomes

  1. Hepatic Glucose Release

    Time frame: 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 outcomes

  1. Hepatic Phosphate Concentrations

    Time frame: 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)

  2. Rates of Lipolysis

    Time frame: 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.

  3. Hepatic Fat Fraction

    Time frame: 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.

  4. Hepatic de Novo Lipogenesis

    Time frame: 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.

Other outcomes

  1. Whole Body Insulin Sensitivity

    Time frame: Measured up to 4 months from enrollment

    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.

  2. Sleep Quality

    Time frame: Measured up to 4 months from enrollment

    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

  3. Sleep Duration

    Time frame: Measured up to 4 months from enrollment

    Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data.

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Collaborators

  • National Center for Advancing Translational Sciences (NCATS)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Official study title

Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls

Acronym: APPLE

Important dates

Study start
2014
Primary completion
2022
Study completion
2022
First posted
Jun 6, 2014
Registry last updated
Jun 4, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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