Post-Prandial Liver Glucose Metabolism in PCOS

NCT ID: NCT03041129

Last Updated: 2024-04-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 19 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-04-14
• Study Completion Date: 2018-09-29

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.

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.

Conditions

Polycystic Ovarian Syndrome; Obesity; Hepatic Steatosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Untreated PCOS

PCOS per NIH criteria. Obese Lifestyle treatment only.

oral glucose tolerance test

Intervention Type: DIAGNOSTIC_TEST

6 hours OGTT

MRI of liver

Intervention Type: DIAGNOSTIC_TEST

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.

oral glucose tolerance test

Intervention Type: DIAGNOSTIC_TEST

6 hours OGTT

MRI of liver

Intervention Type: DIAGNOSTIC_TEST

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.

oral glucose tolerance test

Intervention Type: DIAGNOSTIC_TEST

6 hours OGTT

MRI of liver

Intervention Type: DIAGNOSTIC_TEST

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

oral glucose tolerance test

Intervention Type: DIAGNOSTIC_TEST

6 hours OGTT

MRI of liver

Intervention Type: DIAGNOSTIC_TEST

MRI of the liver and use of DIXON method

Interventions

oral glucose tolerance test

6 hours OGTT

Intervention Type: DIAGNOSTIC_TEST

MRI of liver

MRI of the liver and use of DIXON method

Intervention Type: DIAGNOSTIC_TEST

Eligibility 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

-

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melanie Cree-Green, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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

Aurora, Colorado, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31301251 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

16-2399

Identifier Type: -

Identifier Source: org_study_id