- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02157974
Liver and Fat Regulation in Overweight Adolescent Girls (APPLE)
Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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-
Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado Anshutz Medical Campus/Children's Hospital Colorado
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PCOS, medication naive + Byetta
PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta.
|
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:
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No Intervention: Control
Up to 25 girls without PCOS
|
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No Intervention: PCOS medication naive
Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.
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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.
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No Intervention: PCOS on metformin
Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Measured up to 4 months from enrollment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Measured up to 4 months from enrollment
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Rates of lipolysis
Time Frame: Measured up to 4 months from enrollment
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Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer.
|
Measured up to 4 months from enrollment
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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.
|
Measured up to 4 months from enrollment
|
Hepatic de novo lipogenesis
Time Frame: Measured up to 4 months from enrollment
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Hepatic de novo lipogenesis will be measured by with an acetate tracer.
|
Measured up to 4 months from enrollment
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Lipid Metabolomics: 16n1
Time Frame: Within 4 months from Screening Visit
|
Targeted lipid metabolomics will be performed to measure 16n1
|
Within 4 months from Screening Visit
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Whole Body Insulin Sensitivity
Time Frame: Measured up to 4 months from enrollment
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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.
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Measured up to 4 months from enrollment
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Sleep quality
Time Frame: Measured up to 4 months from enrollment
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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 |
Measured up to 4 months from enrollment
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Sleep duration
Time Frame: Measured up to 4 months from enrollment
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Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data.
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Measured up to 4 months from enrollment
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Stool microbiome profile
Time Frame: Measured up to 4 months from enrollment
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Change in expression of stool microbiome species by comparing the PCOS group to samples collected from a control group without PCOS.
The 5 species with the most significant will be identified and reported from a Manhattan Plot (% rate of appearance): the values above 0 represent species that are greater in the control group than in PCOS and values below 0 represent species that are greater in PCOS than in the control group.
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Measured up to 4 months from enrollment
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Amino Acid Metabolomics: glutamate
Time Frame: Measured up to 4 months from enrollment
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Targeted amino acid metabolomics will be performed to measure glutamate
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Measured up to 4 months from enrollment
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Bile Acid Metabolomics: sphingosine-1-phospate
Time Frame: Measured up to 4 months from enrollment
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Targeted bile acid metabolomics will be performed to measure sphingosine-1-phospate
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Measured up to 4 months from enrollment
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Melanie Cree Green, MD, PhD, Department of Endocrinology
Publications and helpful links
General Publications
- Carreau AM, Pyle L, Garcia-Reyes Y, Rahat H, Vigers T, Jensen T, Scherzinger A, Nadeau KJ, Cree-Green M. Clinical prediction score of nonalcoholic fatty liver disease in adolescent girls with polycystic ovary syndrome (PCOS-HS index). Clin Endocrinol (Oxf). 2019 Oct;91(4):544-552. doi: 10.1111/cen.14062. Epub 2019 Aug 16.
- Simon SL, McWhirter L, Diniz Behn C, Bubar KM, Kaar JL, Pyle L, Rahat H, Garcia-Reyes Y, Carreau AM, Wright KP, Nadeau KJ, Cree-Green M. Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3525-3534. doi: 10.1210/jc.2018-02385.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Endocrine System Diseases
- Ovarian Cysts
- Cysts
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Liver Diseases
- Overnutrition
- Nutrition Disorders
- Body Weight
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Polycystic Ovary Syndrome
- Fatty Liver
- Overweight
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Anti-Obesity Agents
- Incretins
- Exenatide
Other Study ID Numbers
- 14-0542
- UL1TR001082 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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