Post-Prandial Liver Glucose Metabolism in PCOS (PLUM)

• ClinicalTrials.gov Identifier: NCT03041129
• Recruitment Status: Completed
• First Posted: February 2, 2017
• Last Update Posted: February 24, 2020
• Sponsor: University of Colorado, Denver
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

The Investigators will measure if hepatic metabolism is upregulated in obese girls with PCOS and hepatic steatosis (HS), compared to PCOS without HS and obese controls without HS.

Condition or disease	Intervention/treatment
Polycystic Ovarian Syndrome; Obesity; Hepatic Steatosis	Diagnostic Test: oral glucose tolerance test; Diagnostic Test: MRI of liver

Detailed Description:

This will be a cross-sectional study with 4 groups of youth. A 6 hour OSTT (Oral Sugar Tolerance Test) with an oral U-C13 glycerol tracer will be paired with nuclear magnetic resonance spectroscopy (NMR) isotopomer analysis of serum samples to describe flux through the hepatic pentose phosphate pathway, TCA cycle and FAS pathways in girls with PCOS receiving lifestyle only, metformin or oral contraceptive treatment, and obese girls with regular menses receiving lifestyle therapy. Hepatic steatosis will be measured with MRI.

Please note that 3 study groups: PCOS on metformin, PCOS on oral contraceptive treatment, and obese girls with regular menses were not funded in the study, so no participants were enrolled in these 3 arms of the study.

Study Design

• Study Type: Observational
• Actual Enrollment: 19 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• Official Title: Post-Prandial Liver Glucose Metabolism in Polycystic Ovarian Syndrome (PCOS) and Understanding Standard of Care Medications
• Actual Study Start Date: April 14, 2017
• Actual Primary Completion Date: August 29, 2018
• Actual Study Completion Date: September 29, 2018

Groups and Cohorts

Group/Cohort	Intervention/treatment
Untreated PCOS; PCOS per NIH criteria. Obese Lifestyle treatment only.	Diagnostic Test: oral glucose tolerance test; 6 hours OGTT; Diagnostic Test: MRI of liver; MRI of the liver and use of DIXON method
Metformin PCOS-(Study arm not funded); PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months.	Diagnostic Test: oral glucose tolerance test; 6 hours OGTT; Diagnostic Test: MRI of liver; MRI of the liver and use of DIXON method
Oral Contraceptive PCOS-(Study arm not funded); PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months.	Diagnostic Test: oral glucose tolerance test; 6 hours OGTT; Diagnostic Test: MRI of liver; MRI of the liver and use of DIXON method
Obese Control group-(Study arm not funded); Obese Regular menses at least 18 months post-menarche Females only	Diagnostic Test: oral glucose tolerance test; 6 hours OGTT; Diagnostic Test: MRI of liver; MRI of the liver and use of DIXON method

Outcome Measures

Primary Outcome Measures :

1. Hepatic fat fraction [ Time Frame: Within 4 months from Screening Visit ]
   Amount of fat in the liver

Secondary Outcome Measures :

1. Hepatic metabolism ratios [ Time Frame: Within 4 months from Screening Visit ]
   Ratio of pentose phosphate pathway, TCA cycle and fatty acid synthesis metabolites following an OGTT
2. 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.
3. Sleep duration [ Time Frame: Within 4 months from Screening Visit ]
   Sleep duration will be assessed using home actigraphy
4. 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.
5. Stool microbiome profile [ Time Frame: Within 4 months from Screening Visit ]
   Stool microbiome profiles will be determined
6. Hepatic phosphate concentrations [ Time Frame: Within 4 months from Screening Visit ]
   31 phosphorus spectroscopy will be utilized to measure hepatic phosphate concentrations

Biospecimen Retention:   Samples With DNA

DNA for hepatic steatosis related genes

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Females only
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Girls age 12-21. Obese >90th percentile for BMI for age.

Criteria

Inclusion Criteria:

1. Female
2. Ages 12-21
3. Sedentary- less than 2.5 hours of moderate (jogging, swimming etc) exercise a week.
4. BMI equal or greater than the 90th percentile for age and gender

5. For PCOS groups:

   • (NIH definition) irregular menstrual cycles at least 1.5 years after menarche, and
   • either clinical evidence of hyperandogenism, or
   • elevated Testosterone (above the norms for age/tanner stage) at time of screening, or documented prior to initiation of therapy for OCP and metformin groups.

6. For PCOS groups:

   • patients un-treated or currently treated with either Metformin 1500-2000 mg a day, or
   • oral contraception (30-35 mcg ethynyl estradiol a day) for at least 6 months, with > 80% adherence confirmed via refill frequency from pharmacy.

7. For non-PCOS groups:

   • regular menstrual cycles at least 1.5 years after menarche, and
   • no clinical evidence of hyperandrogenism.

Exclusion Criteria:

1. Use of medications known to affect insulin sensitivity:

   • oral glucocorticoids within 10 days,
   • atypical antipsychotics,
   • immunosuppressant agents,
   • HIV medications.
   • Nexplanon, Depo-Provera or Mirena progesterone only contraceptives.
   • Dermal patch or vaginal ring contraception methods.
   • For controls only: metformin or oral contraception.
2. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
3. Severe illness requiring hospitalization within 60 days
4. Diabetes, defined as Hemoglobin A1C > 6.4%
5. BMI percentile less than the 90th percentile for age and sex.
6. Weight >325 lbs or <84 lbs.
7. Anemia, defined as Hemoglobin < 10 mg/dL
8. Diagnosed major psychiatric or developmental disorder limiting informed consent
9. Implanted metal devices that are not compatible with MRI
10. Use of blood pressure medications

11. Known liver disease other than NAFLD or AST or ALT >150 mg/mL

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Contacts and Locations

Locations

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

• Principal Investigator: Melanie Cree-Green, MD, PhD; University of Colorado, Denver

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT03041129
• Other Study ID Numbers: 16-2399
• First Posted: February 2, 2017
• Last Update Posted: February 24, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Colorado, Denver:

hepatic de novo lipogenesis

Additional relevant MeSH terms:

Polycystic Ovary Syndrome; Fatty Liver; Syndrome; Disease; Pathologic Processes; Liver Diseases; Digestive System Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine System Diseases