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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03717935
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

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.

Condition or disease Intervention/treatment Phase
Polycystic Ovarian Syndrome Obesity Hepatic Steatosis Dietary Supplement: Essential Amino Acid (EAA) Supplement Other: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Investigational drug pharmacy will performed randomization and dispense the EAA or placebo.
Primary Purpose: Treatment
Official Title: Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS
Actual Study Start Date : October 8, 2018
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Essential Amino Acid (EAA) Supplement
4 weeks: Essential Amino Acid Supplement- 15g 2/day
Dietary Supplement: Essential Amino Acid (EAA) Supplement
Powder supplement

Placebo Comparator: Placebo
4 weeks: Placebo- 15g 2/day
Other: Placebo
Powder that will be similar to the essential amino acid supplement




Primary Outcome Measures :
  1. Change in 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) ]
    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 :
  1. Change in 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) ]
    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.

  2. Evaluation of Mitochondrial function via change in ratios of direct to indirect hepatic carbon flux in newly synthesized triglycerides [ Time Frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention) ]
    OSTT with UC13 glycerol after each intervention

  3. Change in the hepatic phosphate profile [ 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 via 31 Phosphorus MR spectroscopy after each intervention

  4. Change in 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) ]
    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.

  5. 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) ]
    Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids during the oral glucose tolerance test.

  6. Change in Sleep duration [ Time Frame: 4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention) ]
    Sleep duration will be assessed after each intervention using home actigraphy

  7. Change in 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) ]
    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.

  8. Change in Amino Acid Metabolomics: glutamate, valine, leucine, alanine [ Time Frame: 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

  9. Change in 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) ]
    Targeted lipid metabolomics will be performed after each intervention to look at changes in lipid profiles

  10. Change Bile Acid Metabolomics: sphingosine-1-phospate [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Females
  2. Ages 12-21
  3. Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.
  4. BMI equal or greater than the 90th percentile for age and gender
  5. PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >24 months post-menarche and clinical or biochemical hypertestosteronemia)
  6. HS per FibroScan ultrasound, with CAP score of >225 (will be measured at screening visit)

Exclusion Criteria:

  1. 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.
  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. Weight >325 lbs or <84 lbs.
  6. Anemia, defined as Hemoglobin < 11 mg/dL
  7. Diagnosed major psychiatric or developmental disorder limiting informed consent
  8. Implanted metal devices that are not compatible with MRI
  9. Use of blood pressure medications
  10. Known liver disease other than NAFLD or AST or ALT >125 IU/L

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03717935


Contacts
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Contact: Melanie Cree-Green, MD, PhD 720-777-6128 melanie.green@childrenscolorado.org
Contact: Yesenia Garcia Reyes, MS 720-777-6984 yesenia.garciareyes@childrenscolorado.org

Locations
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United States, Colorado
University of Colorado, Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Melanie Cree-Green, MD, PhD Department of Endocrinology

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03717935    
Other Study ID Numbers: 18-0803
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: March 11, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data will only be shared with IRB approved personnel.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
hepatic de novo lipogenesis
Additional relevant MeSH terms:
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Polycystic Ovary Syndrome
Fatty Liver
Liver Diseases
Digestive System Diseases
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases