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Liver and Fat Regulation in Overweight Adolescent Girls (APPLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02157974
Recruitment Status : Active, not recruiting
First Posted : June 6, 2014
Last Update Posted : August 11, 2022
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 2014
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arms and Interventions
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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 Name: 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
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Primary Outcome Measures :
  1. Hepatic glucose release [ Time Frame: 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 [ Time Frame: Within 4 months from Screening Visit ]
    Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy

  2. Rates of lipolysis [ Time Frame: Within 4 months from Screening Visit ]
    Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer.

  3. Hepatic steatosis [ Time Frame: Within 4 months from Screening Visit ]
    Determination of liver fat content via MRI

  4. Hepatic de novo lipogenesis [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Within 4 months from Screening Visit ]
    Sleep duration will be assessed using home actigraphy

  4. Microbiome [ Time Frame: Within 4 months from Screening Visit ]
    Stool microbiome profiling

  5. Amino Acid Metabolomics: glutamate [ Time Frame: Within 4 months from Screening Visit ]
    Targeted amino acid metabolomics will be performed to measure glutamate

  6. Lipid Metabolomics: 16n1 [ Time Frame: Within 4 months from Screening Visit ]
    Targeted lipid metabolomics will be performed to measure 16n1

  7. Bile Acid Metabolomics: sphingosine-1-phospate [ Time Frame: Within 4 months from Screening Visit ]
    Targeted bile acid metabolomics will be performed to measure sphingosine-1-phospate


Eligibility Criteria
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Ages Eligible for Study:   12 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02157974


Locations
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United States, Colorado
University of Colorado Anshutz Medical Campus/Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Melanie Cree Green, MD, PhD Department of Endocrinology
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02157974    
Other Study ID Numbers: 14-0542
UL1TR001082 ( U.S. NIH Grant/Contract )
First Posted: June 6, 2014    Key Record Dates
Last Update Posted: August 11, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data will only be shared with IRB approved personnel.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polycystic Ovary Syndrome
Fatty Liver
Overweight
Body Weight
Liver Diseases
Digestive System Diseases
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
 Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists