Post-Prandial Liver Glucose Metabolism in PCOS

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03041129

Acronym

PLUM

Enrollment

Registered

2017-02-02

Start date

2017-04-14

Completion date

2018-09-29

Last updated

2024-04-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatic Steatosis, Obesity, Polycystic Ovarian Syndrome

Keywords

hepatic de novo lipogenesis

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.

Interventions

DIAGNOSTIC_TESToral glucose tolerance test

6 hours OGTT

DIAGNOSTIC_TESTMRI of liver

MRI of the liver and use of DIXON method

Study design

Observational model

CASE_CONTROL

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

FEMALE

Age

12 Years to 21 Years

Healthy volunteers

Yes

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 \-

Design outcomes

Primary

Measure	Time frame	Description
Hepatic Fat Fraction	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.

Secondary

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Untreated PCOS PCOS per NIH criteria. Obese Lifestyle treatment only. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method	17
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: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method	0
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: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method	0
Obese Control Group-(Study Arm Not Funded) Obese Regular menses at least 18 months post-menarche Females only oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method	0
Total	17

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Withdrawal by Subject	2	0	0	0

Baseline characteristics

Characteristic	Total	Untreated PCOS	Obese Control Group-(Study Arm Not Funded)	Oral Contraceptive PCOS-(Study Arm Not Funded)	Metformin PCOS-(Study Arm Not Funded)
Age, Continuous	16.2 years STANDARD_DEVIATION 1.68	16.2 years STANDARD_DEVIATION 1.68	—	—	—
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants	10 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants	7 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Region of Enrollment United States	17 participants	17 participants	—	—	—
Sex: Female, Male Female	17 Participants	17 Participants	—	—	—
Sex: Female, Male Male	0 Participants	0 Participants	—	—	—

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 17	0 / 0	0 / 0	0 / 0
other Total, other adverse events	0 / 17	0 / 0	0 / 0	0 / 0
serious Total, serious adverse events	0 / 17	0 / 0	0 / 0	0 / 0

Outcome results

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.