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Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS (ORANGE)

Primary Purpose

Polycystic Ovarian Syndrome, Obesity, Hepatic Steatosis

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Essential Amino Acid (EAA) Supplement

Placebo

About this trial

This is an interventional treatment trial for Polycystic Ovarian Syndrome focused on measuring hepatic de novo lipogenesis

Eligibility Criteria

12 Years - 21 Years (Child, Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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
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

Sites / Locations

University of Colorado, Anschutz Medical Campus

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Essential Amino Acid (EAA) Supplement

Placebo

Arm Description

4 weeks: Essential Amino Acid Supplement- 15g 2/day

4 weeks: Placebo- 15g 2/day

Outcomes

Primary Outcome Measures

Change in Hepatic Fat Fraction

Change from baseline in presence/severity of hepatic fat fraction will be measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%.

Secondary Outcome Measures

Change in Rate of De Novo Lipogenesis

Change from baseline of 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.

Evaluation of Mitochondrial function via change in ratios of direct to indirect hepatic carbon flux in newly synthesized triglycerides

OSTT with UC13 glycerol after each intervention

Change in the hepatic phosphate profile

hepatic phosphate profile via 31 Phosphorus MR spectroscopy after each intervention

Change in Whole Body Insulin Sensitivity

Participants will undergo a 75 gram oral glucose tolerance test, and the change from baseline in whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model.

Change in Adipose Insulin Sensitivity

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

Change in Sleep duration

Sleep duration will be assessed after each intervention using home actigraphy

Change in 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.

Change in Amino Acid Metabolomics: glutamate, valine, leucine, alanine

Targeted amino acid metabolomics will be performed after each intervention

Change in Lipid Metabolomics: 16n1

Targeted lipid metabolomics will be performed after each intervention to look at changes in lipid profiles

Change Bile Acid Metabolomics: sphingosine-1-phospate

Targeted bile acid metabolomics will be performed after each intervention

Full Information

NCT ID

NCT03717935

First Posted

June 15, 2018

Last Updated

March 4, 2022

Sponsor

University of Colorado, Denver

1. Study Identification

Unique Protocol Identification Number

NCT03717935

Brief Title

Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS

Acronym

ORANGE

Official Title

Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

October 8, 2018 (Actual)

Primary Completion Date

January 14, 2022 (Actual)

Study Completion Date

January 14, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Polycystic Ovarian Syndrome, Obesity, Hepatic Steatosis

Keywords

hepatic de novo lipogenesis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Investigational drug pharmacy will performed randomization and dispense the EAA or placebo.

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Essential Amino Acid (EAA) Supplement

Arm Type

Experimental

Arm Description

4 weeks: Essential Amino Acid Supplement- 15g 2/day

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

4 weeks: Placebo- 15g 2/day

Intervention Type

Dietary Supplement

Intervention Name(s)

Essential Amino Acid (EAA) Supplement

Intervention Description

Powder supplement

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Powder that will be similar to the essential amino acid supplement

Primary Outcome Measure Information:

Title

Change in Hepatic Fat Fraction

Description

Change from baseline in presence/severity of hepatic fat fraction will be measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%.

Time Frame

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

Secondary Outcome Measure Information:

Title

Change in Rate of De Novo Lipogenesis

Description

Time Frame