Amino Acid Supplementation in Recovery From Severe Burns (ExAA)

Exercise during recovery is now Standard of Care at Shriners Hospital for Children Galveston, since positive effects of exercise training were found on lean body mass and recovery after burns. Essential amino acids (EAA) effective in healthy individuals.Thus, EAA supplementation in children recovering from burns, may potentially augment the effects of exercise by increase muscle mass, improve muscle fat oxidation, reduce tissue fat, and possibly improve insulin resistance.

Severe burns result in persistent and extensive fat deposition in liver and muscle tissue. This may be related to the prolonged insulin resistance observed following burn. In this study the investigators will test the hypothesis that essential amino acids act in synergy with exercise to improve liver steatosis and muscle lipid metabolism, and thus also affect insulin sensitivity. Children with burns will participate in six weeks of exercise training with/without amino acid supplementation. Before and after the intervention, measurements will be done to determine muscle and liver fat content, muscle fat and protein metabolism, and insulin sensitivity. We will prospectively enroll 40 children with ≥30% of their total body surface area (TBSA) burned. The age range will be 7-17 years. Children will be recruited from Shriners Hospitals for Children (SHC)-Galveston. Burned children will be randomized to undergo an exercise program in combination with daily intake of EAA (n=20) or a placebo drink (n=20). The exercise program and daily intake of AA will begin within the first week of discharge from the burn ICU (approximately 1-3 months post burn, when the patient's wounds are 95% healed). The definition of 95% healed is 7 days after the final autografting procedure. We anticipate enrolling 10 children per year for 4 years. Only children meeting the inclusion and exclusion criteria specified in the Human Subjects Section will be enrolled. Nutritional Supplement: The nutritional supplement will be administered at a dose of 0.18 g/kg body weight of amino acids two times per day with the following composition: 3% histidine, 9% isoleucine, 36% leucine, 17% lysine, 4% methionine, 5% phenylalanine, 10% threonine, 7% valine, and 10% arginine. The dose and choice of amino acids is based on our preliminary data. Each dose is about 0.03 g/kg body weight higher than what has been shown effective in adults, as children have higher protein needs. We have shown that only EAA are needed to affect muscle protein synthesis and lean mass. Thus the amount given (g or kcal) can be restricted. As in our preliminary studies, we will include arginine in the EAA mixture, since arginine may have unique anabolic effects (55; 86). Placebo will consist of a mixture of inert components (sucralose and other pharmaceutical excipients). The supplement will be taken in two daily doses in the form of drinks (total daily dose of i.e., 0.30 g/kg body weight total per day), and intake recorded in a diary. The first dose will be taken between breakfast and lunch, and the second between lunch and dinner. For the children exercising before lunch, the first dose of EAA will be ingested immediately after exercise. Correspondingly, for children exercising after lunch, the second EAA dose of the day will be ingested immediately after exercise. If the child forgets to take one of the drinks during the day, he/she may take the second one between dinner and bedtime. During the weekends, parents/caregivers are instructed to take the dosage around the same time. Data Analysis and Interpretation. To determine effects of amino acids on fat and muscle lipid stores, changes from pre- to post intervention in the two groups will be compared using ANCOVA. From the preliminary data, we expect that amino acids will decrease liver and plasma lipids.

Is the total weight of your body minus all the weight due to your fat mass. It is measured in kilograms by dual X-ray absorptiometry scan.

It is the change in time, from baseline until post exercise. Baseline is within the first week of discharge from the burn ICU, approximately 1-3 months post burn. Exercise training is 6-12 weeks.

A euglycemic-hyperinsulinemic clamp is performed over the last 2hr of the 4-hr isotope infusion. It is measured in μmol/kg body weight/min

It is the change in time, from baseline until post exercise. Baseline is within the first week of discharge from the burn ICU, approximately 1-3 months post burn. Exercise training is 6-12 weeks.

A primed, constant (0.44 μmol/kg/min) infusion of [6,6-2H2]-glucose is used for glucose kinetics. A euglycemic-hyperinsulinemic clamp is performed over the last 2h of the 4-hr isotope infusion.It is measured in μmol/kg body weight/min.

It is the change in time, from baseline until post exercise. Baseline is within the first week of discharge from the burn ICU, approximately 1-3 months post burn. Exercise training is 6-12 weeks.

Inclusion Criteria: Male or female 7-17 years old Body weight >20 kg (based on blood requirements) ≥30% Total Body Surface Area (TBSA) Wounds 95% healed Exclusion Criteria: Respiratory insufficiency Multiple fractures History of Cancer in the last 5 years Diabetes Mellitus Bilirubin > 3 mg/dl Associated head injuries requiring specific therapy Associated injuries to chest or abdomen requiring surgery Serum creatinine > 3 mg/dl after fluid resuscitation Receipt of any experimental drug other than the ones supplied within two months of this study Any metal in body including rods, cardiac defibrillator, pacemakers, etc Orthopedic casting which would prevent placement of patient in MRI machine Hepatitis Abnormal EKG Electrical burns Patients unable to lie still without heavy sedation will be excluded from MRI portion.