Trial Outcomes & Findings for Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS (NCT NCT03717935)

NCT ID: NCT03717935

Last Updated: 2025-03-24

Results Overview

Hepatic Fat Fraction measured after completing placebo and amino acid therapy measured with 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

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 27 participants
• Primary outcome timeframe: 4 weeks after completing the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
• Results posted on: 2025-03-24

Participant Flow

This was a crossover study. There were a total of 27 participants enrolled in the study. Four participants were never randomized: 3 screen failed and 1 of withdrew. Two participants withdrew after completing the placebo phase of the study

Participant milestones

Measure	Essential Amino Acid (EAA) Supplement Followed by Placebo Participants completed: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks washout period and then 4 weeks of Placebo- 15g 2/day.	Placebo Followed by Essential Amino Acid (EAA) Supplement Participants completed: 4 weeks of Placebo- 15g 2/day followed by 4 weeks washout period and then 4 weeks of Essential Amino Acid Supplement- 15g 2/day.
Overall Study STARTED	11	12
Overall Study COMPLETED	11	10
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Essential Amino Acid (EAA) Supplement Followed by Placebo Participants completed: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks washout period and then 4 weeks of Placebo- 15g 2/day.	Placebo Followed by Essential Amino Acid (EAA) Supplement Participants completed: 4 weeks of Placebo- 15g 2/day followed by 4 weeks washout period and then 4 weeks of Essential Amino Acid Supplement- 15g 2/day.
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS

Baseline characteristics by cohort

Measure	All Study Participants: Essential Amino Acid (EAA) Supplement vs Placebo n=27 Participants All study participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo between all participants.
Age, Continuous	15.67 years STANDARD_DEVIATION 1.44 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks after completing the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: adolescent girls with PCOS

Hepatic Fat Fraction measured after completing placebo and amino acid therapy measured with 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

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=21 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Hepatic Fat Fraction After 4 weeks of Placebo	8 percent hepatic fat Interval 4.1 to 15.9
Hepatic Fat Fraction After 4 weeks of EAA	7.3 percent hepatic fat Interval 3.9 to 16.0

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: We were only able to obtain results for this outcome for 19 participants in the study.

The rate of overnight de novo lipogenesis will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction measured after 4 weeks of placebo and after 4 weeks of EAA intervention.

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=19 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Rate of De Novo Lipogenesis After 4 weeks of Placebo	9.60 mg/dL Standard Deviation 6.10
Rate of De Novo Lipogenesis After 4 weeks of EAAs	6.55 mg/dL Standard Deviation 5.52

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Mitochondrial function will be assessed via change in direct hepatic carbon flux in newly synthesized triglycerides (TGs) using an oral sugar tolerance test with an oral UC13 glycerol tracer after each intervention. Data from 180 minutes post-tracer drink is shown below. A higher direct percent means less indirect futile cycling through the TCA cycle.

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=19 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Evaluation of Mitochondrial Function After 4 weeks of Placebo	82.4 percent direct TG synthesis Standard Deviation 2.5
Evaluation of Mitochondrial Function After 4 weeks of EAAs	82.5 percent direct TG synthesis Standard Deviation 2.8

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: We were only able to analyze 18 participants p-31 spectroscopy due to the quality of the spectra.

hepatic phosphate profile via 31 Phosphorus MR spectroscopy after each intervention

Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy after each intervention. The Total phosphate (TP) concentration will be reported after each intervention and the ratio of the following phosphate metabolites will be reported over the 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	Essential Amino Acid (EAA) Supplement vs Placebo n=18 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Hepatic Phosphate Profile After EAA and Placebo Supplement PDE/TP after EAA	0.19670949 Ratio over Total Phosphate Concentration Standard Deviation 0.049409797
Hepatic Phosphate Profile After EAA and Placebo Supplement NADPH/TP after EAA	0.085554177 Ratio over Total Phosphate Concentration Standard Deviation 0.033832954
Hepatic Phosphate Profile After EAA and Placebo Supplement UDPG/TP after Placebo	0.040489089 Ratio over Total Phosphate Concentration Standard Deviation 0.01814369
Hepatic Phosphate Profile After EAA and Placebo Supplement PDE/TP after Placebo	0.186460069 Ratio over Total Phosphate Concentration Standard Deviation 0.034108394
Hepatic Phosphate Profile After EAA and Placebo Supplement PME/TP after EAA	0.073640887 Ratio over Total Phosphate Concentration Standard Deviation 0.036231645
Hepatic Phosphate Profile After EAA and Placebo Supplement PME/TP after Placebo	0.074795509 Ratio over Total Phosphate Concentration Standard Deviation 0.023577971
Hepatic Phosphate Profile After EAA and Placebo Supplement ATP/TP after EAA	0.561426026 Ratio over Total Phosphate Concentration Standard Deviation 0.088487664
Hepatic Phosphate Profile After EAA and Placebo Supplement ATP/TP after Placebo	0.564456782 Ratio over Total Phosphate Concentration Standard Deviation 0.053141701
Hepatic Phosphate Profile After EAA and Placebo Supplement Pi/TP after EAA	0.056107611 Ratio over Total Phosphate Concentration Standard Deviation 0.022628913
Hepatic Phosphate Profile After EAA and Placebo Supplement Pi/TP after Placebo	0.064446077 Ratio over Total Phosphate Concentration Standard Deviation 0.034944194
Hepatic Phosphate Profile After EAA and Placebo Supplement NADPH/TP after Placebo	0.069352473 Ratio over Total Phosphate Concentration Standard Deviation 0.035960915
Hepatic Phosphate Profile After EAA and Placebo Supplement UDPG/TP after EAA	0.02656181 Ratio over Total Phosphate Concentration Standard Deviation 0.017694541

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: Only 20 participants analyzed because the OMM model cannot be run if we have missing insulin or glucose values during the oral sugar tolerance test.

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 4 hour glucose and insulin data during the OGTT after each phase of the study (placebo vs EAA).

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=20 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Whole Body Insulin Sensitivity After 4 weeks of Placebo	0.00026 dl/kg/min per microU/ml Interval 0.0002 to 0.00046
Whole Body Insulin Sensitivity After 4 weeks of EAA	0.00025 dl/kg/min per microU/ml Interval 0.00021 to 0.00043

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: This measure was completed by 22 participants in the placebo phase of the study and 20 in the EAA phase of the study

Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids (FFAs) during the oral glucose tolerance test.

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=22 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Change in Adipose Insulin Sensitivity 4 weeks of Placebo	91.15 percent suppression FFAs Standard Deviation 3.48
Change in Adipose Insulin Sensitivity 4 weeks of EAAs	91.11 percent suppression FFAs Standard Deviation 4.18

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: Out of these 3 participants 2 did not complete their EAA phase for this measurement, so results reported for EAA only include 21 participants.

Sleep duration will be assessed completing placebo and essential amino acid therapy using home actigraphy. Change in sleep duration reported in minutes.

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=21 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Sleep Duration After 4 weeks of placebo	390 minutes Standard Deviation 64
Sleep Duration After 4 weeks of EAA	340.7 minutes Standard Deviation 95.5

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Population: Out of these 3 participants 2 did not complete their EAA phase for this measurement, so results reported for EAA only include 21 participants.

Apnea Hypopnea Index (AHI) will be measured using WatchPAT after each intervention. 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	Essential Amino Acid (EAA) Supplement vs Placebo n=21 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Apnea Hypopnea Index (AHI) After 4 weeks of Placebo	14.99 events per hour Standard Deviation 7.00
Apnea Hypopnea Index (AHI) After 4 weeks of EAA	17.04 events per hour Standard Deviation 8.44

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Targeted amino acid metabolomics will be performed after each intervention and the levels of these 4 amino acids will be reported after each intervention.

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=21 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs Valine after EAAs	284 micro molar Standard Deviation 46
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs Alanine after Placebo	420 micro molar Standard Deviation 120
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs Glutamate after Placebo	49 micro molar Standard Deviation 20
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs Leucine after Placebo	91 micro molar Standard Deviation 16
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs Valine after Placebo	303 micro molar Standard Deviation 36
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs Alanine after EAAs	385 micro molar Standard Deviation 116
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs Glutamate after EAAs	54 micro molar Standard Deviation 21
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs Leucine after EAAs	88 micro molar Standard Deviation 20

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Targeted lipid metabolomics will be performed after each intervention to measure 16n1 lipids after completing 4 weeks of essential amino acid therapy and 4 weeks of placebo.

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=21 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Lipid Metabolomics: 16n1 After 4 weeks of Placebo	87 micro molar Standard Deviation 45
Lipid Metabolomics: 16n1 After 4 weeks of EAAs	88 micro molar Standard Deviation 32

SECONDARY outcome

Timeframe: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)

Targeted bile acid metabolomics will be performed after each intervention to measure levels of sphingosine-1-phospate

Outcome measures

Measure	Essential Amino Acid (EAA) Supplement vs Placebo n=21 Participants Participants completed two 4-week phases of the study in random order with a washout period in between each phase of the study. Each phase consisted of either: 4 weeks of Essential Amino Acid Supplement- 15g 2/day followed by 4 weeks: Placebo- 15g 2/day or vice versa. We are comparing the differences in the essential amino acid vs placebo. Results reported are measured after completing each phase of the study placebo vs EAA
Bile Acid Metabolomics: Sphingosine-1-phospate After 4 Weeks of Placebo and 4 Weeks of EAAs After 4 weeks Placebo	1334 micro molar Standard Deviation 194
Bile Acid Metabolomics: Sphingosine-1-phospate After 4 Weeks of Placebo and 4 Weeks of EAAs After 4 weeks EAAs	1294 micro molar Standard Deviation 281

Adverse Events

All Participants: Essential Amino Acid (EAA) Supplement vs Placebo

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

Phone: 720-777-5743

Email: melanie.green@childrenscolorado.org

Results disclosure agreements

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