Assessment of the Treatment of Severely Burned With Anabolic Agents on Clinical Outcomes, Recovery and Rehabilitation

Study Overview
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Brief Summary
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The purpose of the program is to study and characterize the outcome of burn injury with particular attention to improving the rehabilitation of burn survivors, including children. Various agents are assessed for effectiveness on long term burn outcome, such as growth hormone, oxandrolone, propranolol,ketoconazole, inhospital exercise and home exercise.

Detailed Description
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The University of Texas Medical Branch(UTMB) project improves outcomes for severely burned children by instituting and evaluating two modifications to traditional rehabilitation: (1) an intensive rehabilitation program including active resistance exercise; (2) long term administration of anabolic agents. Effectiveness is assessed by comparison with functional outcomes achieved in traditional outpatient rehabilitation programs. Results indicate improvement in strength, endurance and bone density with these modifications. The project also maintains a longitudinal database that includes measures of cardiopulmonary function, growth and maturation, bone density, range of motion, and psychosocial adjustment.

Official Title
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Assessment of the Treatment of the Severely Burned With Anabolic Agents on Clinical Outcomes, Recovery and Rehabilitation

Conditions
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Burns

Intervention / Treatment
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* Procedure: Stable Isotope Infusion Study
* Procedure: Collection of blood and tissues
* Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI
* Drug: Humatrope
* Drug: Ketoconazole
* Drug: Oxandrolone
* Drug: Propranolol
* Drug: Oxandrolone and propranolol combined
* Drug: Humatrope and propranolol combined
* Drug: Placebo
* Behavioral: Exercise--Hospital supervised intensive exercise program
* Behavioral: Home exercise program


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Burn 30% Total Body Surface Area (TBSA) or greater Ages 0-80 yrs Negative pregnancy test Informed consent Exclusion Criteria: Untreated malignancy, known history of AIDS, Aids Related Complex, HIV Recent history of myocardial infarction (6 wks) Tuberculosis, arthritis, cirrhosis, hyperlipidemia, bone or endocrine diseases, autoimmune diseases Chronic glucocorticoid or non steroidal anti inflammatory drug therapy Diabetes mellitus prior to burn injury Renal insufficiency (defined by creatinine >3.0 mg/dl) Hepatic disease (bilirubin > 3.0 mg/dl)

Ages Eligible for Study
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Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Humatrope subcutaneous(SQ) 0.05-0.2 mg/kg/day for up to 2 years post burn | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Drug: Humatrope<br>* Humatrope (Growth Hormone) dose:0.05mg - 0.2mg/kg/day SQ daily for up to 2 years post burn injury.<br>* Other names: Growth Hormone;|
| Experimental: 2<br>Ketoconazole by mouth (PO) given twice a day throughout hospitalization for up to 2 years post burn | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Drug: Ketoconazole<br>* Ketoconazole administration (or other glucocorticoid blocker--itraconazole or fluconazole) PO daily for up to 2 years post burn injury<br>* Other names: fluconazole;|
| Experimental: 3<br>Oxandrolone PO given daily throughout hospitalization for up to 2 years post burn | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Drug: Oxandrolone<br>* oxandrolone (or other anabolic steroid-testosterone or nandrolone) daily for up to 2 years post burn injury<br>* Other names: nandrolone;|
| Experimental: 4<br>Propranolol PO given daily throughout hospitalization for up to 2 years post burn | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Drug: Propranolol<br>* Propranolol (or other beta adrenergic blocker--metoprolol, inderol), PO administration daily for up to 2 years post burn injury.<br>* Other names: inderol;|
| Experimental: 5<br>Oxandrolone and propranolol PO to be given daily for up to 2 years post burn | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Drug: Oxandrolone and propranolol combined<br>* Daily administration of oxandrolone and propranolol to be given for up to 2 years post burn injury.<br>* Other names: metoprolol;|
| Experimental: 6<br>Humatrope SQ and Propranolol PO to be given daily for up to 2 years post burn | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Drug: Humatrope and propranolol combined<br>* Humatrope (growth hormone) and propranolol administration daily for up to 2 years post burn injury.<br>* Other names: metoprolol;|
| Placebo Comparator: 7<br>Placebo PO to be given for up to 2 years post burn | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Drug: Placebo<br>* placebo to be given once a day for up to two years post burn injury.<br>* Other names: control;|
| Experimental: 8<br>Exercise--hospital supervised intensive exercise program | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Behavioral: Exercise--Hospital supervised intensive exercise program<br>* intensive exercise program supervised by trained personnel in the hospital environment for six up to twelve week program.<br>* Other names: hospital based exercise;|
| Experimental: 9<br>Exercise--home or community based exercise program | Procedure: Stable Isotope Infusion Study<br>* 1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.<br>Procedure: Collection of blood and tissues<br>* Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study<br>Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI<br>* Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.<br>Behavioral: Home exercise program<br>* Home intensive exercise program: training occurs in hospital then patient sent home to continue exercise program for six weeks and up to 12 weeks at home.<br>* Other names: exercise rehabilitation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measures of muscle wasting, weakness, immunosuppression chronic bone loss and decreased growth with increases in metabolic, hemodynamic, inflammatory and scarring responses. | Dual Energy X-Ray Absorptiometry measurements will be utilized to measure muscle wasting | Admission to burn unit and up to 2 years post burn and yearly after that | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anabolic agents, exercise