APPLE: Liver and Fat Regulation in Overweight Adolescent Girls

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02157974
• Collaborator: (none)
• Enrollment: 105
• Location: 1
• Arms: 5
• Anticipated Duration (Months): 100
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Steatosis; Polycystic Ovarian Syndrome; Obesity	Drug: Byetta 5Mcg Pen Injection	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 105 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls
• Actual Study Start Date: Aug 1, 2014
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PCOS, medication naive + Byetta PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta.	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; Other Names: Exenatide
No Intervention: Control Up to 25 girls without PCOS
No Intervention: PCOS medication naive Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.
No Intervention: PCOS on COCPs Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.
No Intervention: PCOS on metformin Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures

Outcome Measures

Primary Outcome Measures

1. Hepatic glucose release [Within 4 months from Screening Visit]

   Hepatic glucose release will be measured by the rate of appearance of a glucose tracer.

Secondary Outcome Measures

1. Hepatic phosphate concentrations [Within 4 months from Screening Visit]

   Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy

2. Rates of lipolysis [Within 4 months from Screening Visit]

   Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer.

3. Hepatic steatosis [Within 4 months from Screening Visit]

   Determination of liver fat content via MRI

4. Hepatic de novo lipogenesis [Within 4 months from Screening Visit]

   Hepatic de novo lipogenesis will be measured by with an acetate tracer.

Other Outcome Measures

1. Whole Body Insulin Sensitivity [Within 4 months from Screening Visit]

   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.

2. Sleep quality [Within 4 months from Screening Visit]

   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.

3. Sleep duration [Within 4 months from Screening Visit]

   Sleep duration will be assessed using home actigraphy

4. Microbiome [Within 4 months from Screening Visit]

   Stool microbiome profiling

5. Amino Acid Metabolomics: glutamate [Within 4 months from Screening Visit]

   Targeted amino acid metabolomics will be performed to measure glutamate

6. Lipid Metabolomics: 16n1 [Within 4 months from Screening Visit]

   Targeted lipid metabolomics will be performed to measure 16n1

7. Bile Acid Metabolomics: sphingosine-1-phospate [Within 4 months from Screening Visit]

   Targeted bile acid metabolomics will be performed to measure sphingosine-1-phospate

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 21 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Anshutz Medical Campus/Children's Hospital Colorado	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Melanie Cree Green, MD, PhD, Department of Endocrinology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02157974
• Other Study ID Numbers: 14-0542; UL1TR001082
• First Posted: Jun 6, 2014
• Last Update Posted: Aug 11, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Fatty Liver; Overweight; Exenatide

Study Results

No Results Posted as of Aug 11, 2022