Post-Prandial Liver Glucose Metabolism in PCOS

Obesity Clinical Trial

— PLUM  

Official title:

Post-Prandial Liver Glucose Metabolism in Polycystic Ovarian Syndrome (PCOS) and Understanding Standard of Care Medications

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03041129
• Other study ID #: 16-2399
• Status: Completed
• Start date: April 14, 2017
• Est. completion date: September 29, 2018

Study information

• Verified date: April 2024
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: September 29, 2018
• Est. primary completion date: August 29, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 12 Years to 21 Years

Eligibility

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 -

Related Conditions & MeSH terms

• Fatty Liver
• Hepatic Steatosis
• Obesity
• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Diagnostic Test:
• oral glucose tolerance test
6 hours OGTT
• MRI of liver
MRI of the liver and use of DIXON method

Locations

Country	Name	City	State
United States	University of Colorado Anshutz Medical Campus/Children's Hospital Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hepatic Fat Fraction	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
Secondary	Hepatic Metabolism Ratios	Percent indirect glucose at 360 minutes following an oral sugar tolerance test (OGTT) with an isotope labeled oral glycerol tracer.	Measured up to 4 months from enrollment
Secondary	Whole Body Insulin Sensitivity	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.	Measured up to 4 months from enrollment
Secondary	Sleep Duration	Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data.	Measured up to 4 months from enrollment
Secondary	Sleep Quality	Apnea Hypopnea Index (AHI) will be measured using WatchPAT. 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
Secondary	Hepatic Phosphate Concentrations	31 phosphorus spectroscopy will be utilized to measure hepatic Phosphodiesterase (PDE)/Total phosphate concentration. This is measured in the MRI using a phosphorus coil.	Measured up to 4 months from enrollment