Oral Amino Acid Nutrition to Improve Glucose Excursions in PCOS
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Hepatic Fat Fraction
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Investigational drug pharmacy will performed randomization and dispense the EAA or placebo.
入排标准
- 年龄范围
- 12 Years 至 21 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
结局指标
主要结局
Hepatic Fat Fraction
时间窗: 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
次要结局
- Amino Acid Metabolomics: Alanine, Glutamate, Leucine, Valine Levels After 4 Weeks of Placebo and 4 Weeks of EAAs(4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention))
- Lipid Metabolomics: 16n1(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(4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention))
- Rate of De Novo Lipogenesis(4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention))
- Evaluation of Mitochondrial Function(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(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(4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention))
- Apnea Hypopnea Index (AHI)(4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention))
- Whole Body Insulin Sensitivity(4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention))
- Sleep Duration(4 weeks after the first intervention, and approximately 8 weeks later (4 weeks washout and 4 weeks of second intervention))