Polycystic Ovarian SyndromeORANGENCT03717935
Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS
A study testing Essential Amino Acid (EAA) Supplement in people with Polycystic Ovarian Syndrome and Obesity, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The Investigators will measure hepatic glucose and fat metabolism in obese girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) after taking 4 weeks of an essential amino acid (EAA) supplement or placebo and test whether the EAA supplement can improve hepatic glucose metabolism in these girls. Read more about this study
- Who is it for?
- Ages 12 to 21 years, women only
- Conditions the study is for
- Polycystic Ovarian Syndrome, Obesity, Hepatic Steatosis
- What is being tested?
- Essential Amino Acid (EAA) Supplement
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2018to 14 Jan 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 21 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Females
- Ages 12-21
- Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.
- BMI equal or greater than the 90th percentile for age and gender
- PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >24 months post-menarche and clinical or biochemical hypertestosteronemia)
- HS per FibroScan ultrasound, with CAP score of >225 (will be measured at screening visit)
Who cannot join
- Use of medications known to affect insulin sensitivity: metformin, oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, hormonal contraception. Dermal patch or vaginal ring contraception methods.
- Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
- Severe illness requiring hospitalization within 60 days
- Diabetes, defined as Hemoglobin A1C > 6.4%
- BMI percentile less than the 90th percentile for age and sex. Weight >325 lbs or <84 lbs.
- Anemia, defined as Hemoglobin < 11 mg/dL
Show all 10Show fewer
- Diagnosed major psychiatric or developmental disorder limiting informed consent
- Implanted metal devices that are not compatible with MRI
- Use of blood pressure medications
- Known liver disease other than NAFLD or AST or ALT >125 IU/L
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado, Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
The Investigators will measure hepatic glucose and fat metabolism in obese girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) after taking 4 weeks of an essential amino acid (EAA) supplement or placebo and test whether the EAA supplement can improve hepatic glucose metabolism in these girls.
Read the detailed description
Girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) will complete a 12 week double-blinded placebo controlled cross-over study with 4 weeks each of an essential amino acid (EAA) supplement and placebo, and will complete metabolic studies after each intervention. There will be a 4 week wash out period in-between. The metabolic tests after each intervention (EAA/placebo) will include an oral sugar tolerance test (OSTT) and an oral U-C13 glycerol tracer that is paired with Nuclear Magnetic Resonance (NMR) isotopomer analysis of serum samples to describe flux through the hepatic pentose phosphate pathway, tricarboxylic acid (TCA) cycle and fatty acid synthesis pathways in girls with PCOS and HS. Hepatic steatosis will be measured with magnetic resonance Imaging (MRI) and hepatic phosphate concentrations with magnetic resonance (MR) spectroscopy.
- Conditions
- Polycystic Ovarian Syndrome, Obesity, Hepatic Steatosis
- Being tested
- Essential Amino Acid (EAA) Supplement, Placebo
- Keywords
- hepatic de novo lipogenesis
- Medical subject headings
- Polycystic Ovary Syndrome, Obesity, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Essential Amino Acid (EAA) SupplementDietary supplement
Powder supplement
PlaceboOther
Powder that will be similar to the essential amino acid supplement
| Study group | Role | What they receive |
|---|---|---|
| Essential Amino Acid (EAA) Supplement | Experimental | 4 weeks: Essential Amino Acid Supplement- 15g 2/day Receives: Dietary Supplement: Essential Amino Acid (EAA) Supplement; Other: Placebo |
| Placebo | Placebo comparator | 4 weeks: Placebo- 15g 2/day Receives: Dietary Supplement: Essential Amino Acid (EAA) Supplement; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic Fat Fraction
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
Measured: 4 weeks after completing the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Secondary outcomes (10)
Rate of De Novo Lipogenesis
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.
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Evaluation of Mitochondrial Function
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.
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Hepatic Phosphate Profile After EAA and Placebo Supplement
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)
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
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 using 4 hour glucose and insulin data during the OGTT after each phase of the study (placebo vs EAA).
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Change in Adipose Insulin Sensitivity
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.
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Sleep Duration
Sleep duration will be assessed completing placebo and essential amino acid therapy using home actigraphy. Change in sleep duration reported in minutes.
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Apnea Hypopnea Index (AHI)
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
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs
Targeted amino acid metabolomics will be performed after each intervention and the levels of these 4 amino acids will be reported after each intervention.
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Lipid Metabolomics: 16n1
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.
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Bile Acid Metabolomics: Sphingosine-1-phospate After 4 Weeks of Placebo and 4 Weeks of EAAs
Targeted bile acid metabolomics will be performed after each intervention to measure levels of sphingosine-1-phospate
Measured: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2018
- Study start8 Oct 2018
- Primary completion14 Jan 2022
- Study completion14 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovarian SyndromeStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Melanie Cree-Green, MD, PhD, Principal investigator, Department of Endocrinology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03717935
- Sponsor's protocol ID
- 18-0803
- Acronym
- ORANGE
- Status last verified
- Mar 2025
- First submitted
- 15 Jun 2018
- Last updated
- 24 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data will only be shared with IRB approved personnel.
Publications
Boster JM, Cree MG, Kelsey MM, Nadeau KJ, Chaidez A, Pan Z, Sundaram SS. Relative Skeletal Muscle Mass Is Associated With Hepatic Steatosis in Adolescents With Overweight and Obesity. Pediatr Obes. 2026 Apr;21(4):e70108. doi: 10.1111/ijpo.70108.
PubMed 42014131
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS
- ClinicalTrials.gov ID
- NCT03717935
- Acronym / sponsor ID
- ORANGE / 18-0803
- Conditions
- Polycystic Ovarian Syndrome, Obesity, Hepatic Steatosis
- Keywords
- hepatic de novo lipogenesis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 8 Oct 2018 (actual)
- Primary completion
- 14 Jan 2022 (actual)
- Study completion
- 14 Jan 2022 (actual)
- First posted
- 24 Oct 2018 (actual)
- Results
- Posted 24 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Investigators will measure hepatic glucose and fat metabolism in obese girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) after taking 4 weeks of an essential amino acid (EAA) supplement or placebo and test whether the EAA supplement can improve hepatic glucose metabolism in these girls.
Detailed description
Girls with Polycystic Ovarian Syndrome (PCOS) and hepatic steatosis (HS) will complete a 12 week double-blinded placebo controlled cross-over study with 4 weeks each of an essential amino acid (EAA) supplement and placebo, and will complete metabolic studies after each intervention. There will be a 4 week wash out period in-between. The metabolic tests after each intervention (EAA/placebo) will include an oral sugar tolerance test (OSTT) and an oral U-C13 glycerol tracer that is paired with Nuclear Magnetic Resonance (NMR) isotopomer analysis of serum samples to describe flux through the hepatic pentose phosphate pathway, tricarboxylic acid (TCA) cycle and fatty acid synthesis pathways in girls with PCOS and HS. Hepatic steatosis will be measured with magnetic resonance Imaging (MRI) and hepatic phosphate concentrations with magnetic resonance (MR) spectroscopy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Essential Amino Acid (EAA) Supplement | Experimental | Dietary Supplement: Essential Amino Acid (EAA) Supplement, Other: Placebo4 weeks: Essential Amino Acid Supplement- 15g 2/day |
| Placebo | Placebo comparator | Dietary Supplement: Essential Amino Acid (EAA) Supplement, Other: Placebo4 weeks: Placebo- 15g 2/day |
Who may qualify
- Ages
- 12 to 21 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Females
- Ages 12-21
- Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.
- BMI equal or greater than the 90th percentile for age and gender
- PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >24 months post-menarche and clinical or biochemical hypertestosteronemia)
Key exclusion criteria (10 listed)
- Use of medications known to affect insulin sensitivity: metformin, oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, hormonal contraception. Dermal patch or vaginal ring contraception methods.
- Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
- Severe illness requiring hospitalization within 60 days
- Diabetes, defined as Hemoglobin A1C > 6.4%
- BMI percentile less than the 90th percentile for age and sex. Weight >325 lbs or <84 lbs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Essential Amino Acid (EAA) SupplementPowder supplement | Dietary supplement | Essential Amino Acid (EAA) Supplement, Placebo |
| PlaceboPowder that will be similar to the essential amino acid supplement | Other | Essential Amino Acid (EAA) Supplement, Placebo |
Primary outcome
Hepatic Fat Fraction
Time frame: 4 weeks after completing the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
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
10 secondary outcomes
Rate of De Novo Lipogenesis
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Evaluation of Mitochondrial Function
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Hepatic Phosphate Profile After EAA and Placebo Supplement
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Whole Body Insulin Sensitivity
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Change in Adipose Insulin Sensitivity
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Sleep Duration
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Apnea Hypopnea Index (AHI)
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Lipid Metabolomics: 16n1
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Bile Acid Metabolomics: Sphingosine-1-phospate After 4 Weeks of Placebo and 4 Weeks of EAAs
Time frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42014131Boster JM, Cree MG, Kelsey MM, Nadeau KJ, Chaidez A, Pan Z, Sundaram SS. Relative Skeletal Muscle Mass Is Associated With Hepatic Steatosis in Adolescents With Overweight and Obesity. Pediatr Obes. 2026 Apr;21(4):e70108. doi: 10.1111/ijpo.70108.
- Individual participant dataSharing planned: No. Data will only be shared with IRB approved personnel.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melanie Cree-Green, MD, PhD principal investigator
Department of Endocrinology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Essential Amino Acid (EAA) Supplement in people with Polycystic Ovarian Syndrome and Obesity, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic Fat Fraction (time frame: 4 weeks after completing the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03717935, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.