Effects of Amino Acid Supplementation on Liver Lipid Content and Protein Metabolism in Obese Children

Not Applicable

• Conditions: Liver Steatosis; Whole Body Protein Metabolism; Body Composition, Beneficial; Insulin Resistance
• Interventions: Dietary Supplement: Placebo; Dietary Supplement: Essential amino acids plus arginine

• Registration Number: NCT02337894
• Lead Sponsor: Arkansas Children's Hospital Research Institute

Brief Summary

The purpose of this study is to assess the effect of an eight-week dietary supplementation with essential amino acids plus arginine on liver and plasma lipid content, whole-body fat oxidation, whole-body insulin sensitivity, whole body protein metabolism, and body composition in obese pre-pubertal children.

Detailed Description

Up to thirty-two obese pre-pubertal children will be recruited for this study. Up to sixteen will be boys and up to sixteen will be girls. The study will be a double-blinded, placebo-controlled trial using a randomized, but counter-balanced design. This will ensure equal numbers in the two groups that the children are randomized to, for each sex. The control group will receive placebo and the intervention group will receive essential amino acids plus arginine. The supplements (essential amino acids plus arginine, and placebo) will be given in the form of a drink twice a day for a total of 8 weeks. Both the participants and the investigators will be blinded to group assignment.

The primary endpoints of this study are to assess the effect of essential amino acids (EAA) plus arginine supplementation on lipid and protein metabolism. For this, liver lipid content, hepatic apoptosis, plasma lipids, apolipoprotein B-100 (apo B-100) levels, hepatic fatty oxidation, whole body insulin sensitivity, body composition and whole body protein turnover. will be compared between the intervention and placebo groups.

Study Timeline

• Study First Submitted: 2014-12-02
• Study First Submitted QC: 2015-01-09
• Study First Posted: 2015-01-14
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-12
• Last Update Posted: 2021-01-13
• Study Start: 2022-01-30
• Primary Completion: 2023-02
• Study Completion: 2023-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Healthy boy or girl
• Age 7-10 years of age and Tanner stage no greater than stage 1
• BMI ≥ 95th percentile
• Not participating for more than 1 hour/week in a regular physical activity program

Exclusion Criteria

• Tanner stage greater than stage 1
• Having known chronic illnesses/disorders that may independently affect study outcome measures: type 2 or type 1 diabetes mellitus, neurologic (e.g. epilepsy), neurobehavioral (e.g. Attention deficit disorder and hyperactivity, ADHD) endocrine, hepatic, autoimmune, cardiac and renal disorders. Also, chronic lung disorders except well controlled asthma that does not require permanent use of inhaled/oral steroids
• Taking permanent medications: thyroid hormone replacement therapy, inhaled/oral steroids, insulin, metformin, anabolic drugs (growth hormone replacement therapy and oxandrolone) anti-lipid medication, blood pressure medication, ADHD medication (methylphenidate, amphetamines, atomoxetine)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control drink	Placebo	The control drinks will be indistinguishable from the intervention drinks in taste and volume, but will contain placebo rather than essential amino acids plus arginine.
Essential amino acids plus arginine	Essential amino acids plus arginine	Children randomized to the intervention group will receive a supplement containing essential amino acids plus arginine in the form of a drink which they will have to take for 8 weeks. Measurement of liver lipid content, hepatic apoptosis, plasma lipids, apolipoprotein B-100 levels, hepatic fatty oxidation, whole body insulin sensitivity, body composition and whole body protein turnover will be compared with the the placebo group, and before and after the intervention.

Primary Outcome Measures

Name	Time	Method
Serum levels of markers of lipid metabolism before and after 8 weeks of supplementation with essential amino acids plus arginine vs placebo.	Baseline and 8 weeks	Change in serum levels of triglycerides, cholesterol, very low density lipoprotein (VLDL), low density lipoprotein (LDL), beta-hydroxybutyrate, Apo-lipoprotein B and plasma cytokeratin 18 will be assessed after 8 weeks of essential amino acids plus arginine vs placebo.
Whole body protein turnover before and after 8 weeks of supplementation with essential amino acids plus arginine vs. placebo.	Baseline and 8 weeks	Change in whole body protein metabolism (synthesis and breakdown) following 8 weeks of essential amino acids plus arginine vs placebo. This outcome will be assessed using a stable isotope of an amino acid (15N-alanine).
Liver lipid content before and after 8 weeks of supplementation with essential amino acids plus arginine vs placebo.	Baseline and 8 weeks	Nuclear Magnetic Resonance Spectroscopy will be used to assess changes in liver lipid content following an 8-week supplementation period with essential amino acids plus arginine vs. placebo.
Body composition before and after 8 weeks of supplementation with essential amino acids plus arginine vs. placebo.	Baseline and 8 weeks	Changes in body composition (fat free mass and fat mass) will be assessed using Dual-Energy X-ray Absorptiometry. Measurements will be carried out at baseline and following 8 weeks of supplementation with essential amino acids plus arginine vs. placebo.

Secondary Outcome Measures

Name	Time	Method
HOMA-IR index before and after 8 weeks of supplementation with essential amino acids plus arginine vs placebo.	Baseline and 8 weeks	Fasting glucose and insulin levels will be used to assess changes in the HOMA-IR index after 8 weeks of supplementation with essential amino acids plus arginine vs. placebo.