Trial Outcomes & Findings for Liver and Fat Regulation in Overweight Adolescent Girls (NCT NCT02157974)

NCT ID: NCT02157974

Last Updated: 2024-06-04

Results Overview

Hepatic glucose release will be measured by the rate of appearance of a glucose tracer. Glucose rate of appearance reflects the amount of glucose being release by primarily the liver during fasting. A higher glucose rate of appearance is often seen with dysglycemia

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 92 participants
• Primary outcome timeframe: Measured up to 4 months from enrollment
• Results posted on: 2024-06-04

Participant Flow

Participant milestones

Measure	Control Up to 25 girls without PCOS. No participants received an intervention in this specific study.	PCOS Medication Naive Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months. No participants received an intervention in this specific study.	PCOS, Medication Naive + Byetta PCOS, medication naive; These 10 participants received 2 doses of Byetta during their metabolic visit prior to the oral glucose tolerance testing. These participants recieved Byetta 5Mcg Pen Injection: 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	PCOS on COCPs Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures. No participants received an intervention in this specific study.	PCOS on Metformin Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures No participants received an intervention in this specific study.
Overall Study STARTED	24	42	10	10	6
Overall Study COMPLETED	24	39	10	10	6
Overall Study NOT COMPLETED	0	3	0	0	0

Reasons for withdrawal

Measure	Control Up to 25 girls without PCOS. No participants received an intervention in this specific study.	PCOS Medication Naive Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months. No participants received an intervention in this specific study.	PCOS, Medication Naive + Byetta PCOS, medication naive; These 10 participants received 2 doses of Byetta during their metabolic visit prior to the oral glucose tolerance testing. These participants recieved Byetta 5Mcg Pen Injection: 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	PCOS on COCPs Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures. No participants received an intervention in this specific study.	PCOS on Metformin Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures No participants received an intervention in this specific study.
Overall Study Withdrawal by Subject	0	1	0	0	0
Overall Study Screen Failure	0	1	0	0	0
Overall Study Nurse not able to place IV so unable to complete visit	0	1	0	0	0

Baseline Characteristics

Liver and Fat Regulation in Overweight Adolescent Girls

Baseline characteristics by cohort

Measure	Control n=24 Participants Up to 25 girls without PCOS	PCOS Medication Naive n=42 Participants Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=10 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=10 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=6 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures	Total n=92 Participants Total of all reporting groups
Age, Categorical <=18 years	23 Participants n=5 Participants	34 Participants n=7 Participants	7 Participants n=5 Participants	9 Participants n=4 Participants	6 Participants n=21 Participants	79 Participants n=10 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	8 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	13 Participants n=10 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Age, Continuous	15.3 years STANDARD_DEVIATION 1.62 • n=5 Participants	15.9 years STANDARD_DEVIATION 1.81 • n=7 Participants	15.3 years STANDARD_DEVIATION 2.16 • n=5 Participants	15.7 years STANDARD_DEVIATION 1.34 • n=4 Participants	15.6 years STANDARD_DEVIATION 1.7 • n=21 Participants	15.62 years STANDARD_DEVIATION 1.73 • n=10 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	42 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	6 Participants n=21 Participants	92 Participants n=10 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	20 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	48 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	22 Participants n=7 Participants	7 Participants n=5 Participants	4 Participants n=4 Participants	2 Participants n=21 Participants	44 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Region of Enrollment United States	24 participants n=5 Participants	42 participants n=7 Participants	10 participants n=5 Participants	10 participants n=4 Participants	6 participants n=21 Participants	92 participants n=10 Participants

PRIMARY outcome

Timeframe: Measured up to 4 months from enrollment

Population: Not all participants had complete data to analyze the glucose RA.

Hepatic glucose release will be measured by the rate of appearance of a glucose tracer. Glucose rate of appearance reflects the amount of glucose being release by primarily the liver during fasting. A higher glucose rate of appearance is often seen with dysglycemia

Outcome measures

Measure	Control n=16 Participants Up to 25 girls without PCOS	PCOS Medication Naive n=30 Participants Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=9 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=8 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=4 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Hepatic Glucose Release	1.85 mg/kg/min Standard Deviation 1.24	1.46 mg/kg/min Standard Deviation 0.21	1.54 mg/kg/min Standard Deviation 0.38	1.88 mg/kg/min Standard Deviation 0.49	1.57 mg/kg/min Standard Deviation 0.07

SECONDARY outcome

Timeframe: Measured up to 4 months from enrollment

Population: The phosphorus coil for the liver was purchased towards the end of the study, so not all participants had the 31p measured.

Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy. The ratio of the following will be reported over total phosphate concentration: Phosphodiesterase (PDE), phosphomonoester (PME), Adenosine triphosphate (ATP), Inorganic Phosphate (Pi),Nicotinamide adenine dinucleotide phosphate (NADPH), Uridine diphosphate glucose (UDPG)

Outcome measures

Measure	Control n=5 Participants Up to 25 girls without PCOS	PCOS Medication Naive Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=8 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=9 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=6 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Hepatic Phosphate Concentrations PDE/TP	0.167684728 ratio over total phosphate Standard Deviation 0.056413082	—	0.198640255 ratio over total phosphate Standard Deviation 0.040933351	0.198787476 ratio over total phosphate Standard Deviation 0.045832565	0.186923469 ratio over total phosphate Standard Deviation 0.039481266
Hepatic Phosphate Concentrations PME/TP	0.067905319 ratio over total phosphate Standard Deviation 0.033816456	—	0.077949656 ratio over total phosphate Standard Deviation 0.02943916	0.075872089 ratio over total phosphate Standard Deviation 0.024970918	0.066789803 ratio over total phosphate Standard Deviation 0.036986035
Hepatic Phosphate Concentrations ATP/TP	0.592517535 ratio over total phosphate Standard Deviation 0.038294886	—	0.566952309 ratio over total phosphate Standard Deviation 0.061717281	0.565157308 ratio over total phosphate Standard Deviation 0.042119495	0.557277652 ratio over total phosphate Standard Deviation 0.034367129
Hepatic Phosphate Concentrations Pi/TP	0.041945761 ratio over total phosphate Standard Deviation 0.02076513	—	0.054581135 ratio over total phosphate Standard Deviation 0.019288097	0.046604505 ratio over total phosphate Standard Deviation 0.022669904	0.074459672 ratio over total phosphate Standard Deviation 0.021584936
Hepatic Phosphate Concentrations NADPH/TP	0.097201285 ratio over total phosphate Standard Deviation 0.043438464	—	0.068550332 ratio over total phosphate Standard Deviation 0.028503778	0.067305736 ratio over total phosphate Standard Deviation 0.033620062	0.074693726 ratio over total phosphate Standard Deviation 0.021031863
Hepatic Phosphate Concentrations UDPG/TP	0.032745372 ratio over total phosphate Standard Deviation 0.011777685	—	0.033326313 ratio over total phosphate Standard Deviation 0.014030497	0.046272886 ratio over total phosphate Standard Deviation 0.023894603	0.039855678 ratio over total phosphate Standard Deviation 0.012418624

SECONDARY outcome

Timeframe: Measured up to 4 months from enrollment

Population: Not all participants had complete data to analyze the glycerol RA.

Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer. Glycerol rate of appearance reflects the amount of glycerol being released into the blood stream as a results of lipolysis. Higher rates of lipolysis are thought to be associated with insulin resistance.

Outcome measures

Measure	Control n=18 Participants Up to 25 girls without PCOS	PCOS Medication Naive n=32 Participants Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=10 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=10 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=6 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Rates of Lipolysis	0.54 mg/kg/min Standard Deviation 0.17	0.49 mg/kg/min Standard Deviation 0.22	0.49 mg/kg/min Standard Deviation 0.24	0.78 mg/kg/min Standard Deviation 0.18	0.65 mg/kg/min Standard Deviation 0.19

SECONDARY outcome

Timeframe: Measured up to 4 months from enrollment

Population: Unable to analyze 2 participants in the PCOS medication naive group. One screen failed and the second who withdrew from the study.

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.

Outcome measures

Measure	Control n=24 Participants Up to 25 girls without PCOS	PCOS Medication Naive n=40 Participants Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=10 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=10 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=6 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Hepatic Fat Fraction	4.1 percent fat Standard Deviation 3.1	7.6 percent fat Standard Deviation 6.3	6.9 percent fat Standard Deviation 5.3	6.8 percent fat Standard Deviation 9.4	13.3 percent fat Standard Deviation 12.1

SECONDARY outcome

Timeframe: Measured up to 4 months from enrollment

Population: Not everyone in the study received the acetate tracer. We had a problem with the analysis of the acetate tracer on 3 participants: 1 from the control group and 2 from the metformin group, so we did not obtain data for those 3 participants.

Hepatic de novo lipogenesis will be measured by with an acetate tracer by mass spectroscopy. De novo lipogenesis can contribute to non-alcoholic fatty liver disease, so having a lower value is better.

Outcome measures

Measure	Control n=9 Participants Up to 25 girls without PCOS	PCOS Medication Naive n=12 Participants Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=10 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=5 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=3 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Hepatic de Novo Lipogenesis	9.3 mg/dL Standard Deviation 5.3	6.6 mg/dL Standard Deviation 4.2	7.9 mg/dL Standard Deviation 7.2	18.2 mg/dL Standard Deviation 14.9	19.4 mg/dL Standard Deviation 17.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Measured up to 4 months from enrollment

Population: We were unable to calculate Si for some of the participants, because we were missing some lab values that are required for the formula.

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 using SAMM II software. This software uses participant weight, glucose and insulin concentrations at various time points during the oral glucose tolerance test to calculate the participant insulin sensitivity. The higher the Si value means more insulin sensitivity.

Outcome measures

Measure	Control n=23 Participants Up to 25 girls without PCOS	PCOS Medication Naive n=33 Participants Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=10 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=10 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=6 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Whole Body Insulin Sensitivity	0.000319383 dL/kg/min/μU/mL Standard Deviation 0.00021025	0.00021077 dL/kg/min/μU/mL Standard Deviation 0.000275814	0.00033516 dL/kg/min/μU/mL Standard Deviation 0.000366279	0.00021791 dL/kg/min/μU/mL Standard Deviation 0.000255919	0.0000959833333 dL/kg/min/μU/mL Standard Deviation 0.0000414436685

OTHER_PRE_SPECIFIED outcome

Timeframe: Measured up to 4 months from enrollment

Population: The WatchPAT device was purchased towards the end of the study, so this was only used on a few participants for which results are reported here.

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

Outcome measures

Measure	Control n=2 Participants Up to 25 girls without PCOS	PCOS Medication Naive Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=2 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=5 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=2 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Sleep Quality	9.15 Apnea Hypopnea Index Standard Deviation 4.71	—	31.25 Apnea Hypopnea Index Standard Deviation 12.09	19.32 Apnea Hypopnea Index Standard Deviation 11.85	19 Apnea Hypopnea Index Standard Deviation 0.57

OTHER_PRE_SPECIFIED outcome

Timeframe: Measured up to 4 months from enrollment

Population: Watch failed to record data on: 3 participants in the control group, 2 in the PCOS medication naive group, and 1 in the Byetta group. Two participants withdrew from the PCOS medication naive group.

Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data.

Outcome measures

Measure	Control n=21 Participants Up to 25 girls without PCOS	PCOS Medication Naive n=38 Participants Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.	PCOS, Medication Naive + Byetta n=9 Participants PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 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	PCOS on COCPs n=10 Participants Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.	PCOS on Metformin n=6 Participants Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures
Sleep Duration	430.85 minutes Standard Deviation 48.38	437.88 minutes Standard Deviation 49.32	410.3 minutes Standard Deviation 58	438.29 minutes Standard Deviation 49.76	414.87 minutes Standard Deviation 62.29

Adverse Events

Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PCOS Medication Naive

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PCOS, Medication Naive + Byetta

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PCOS on COCPs

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

PCOS on Metformin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Melanie Cree-Green, PI

University of Colorado Anschutz Medical Campus

Phone: 720-777-5743

Email: melanie.green@childrenscolorado.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place