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

Sponsor

The University of Texas Medical Branch, Galveston (Other)

Overall Status

Terminated

CT.gov ID

NCT00675714

Collaborator

U.S. Department of Education (U.S. Fed), National Institutes of Health (NIH) (NIH), National Institute of General Medical Sciences (NIGMS) (NIH)

1,126

Enrollment

Location

Arms

186.4

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Burns	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	Phase 2/Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1126 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2004

Actual Primary Completion Date :

Sep 1, 2018

Actual Study Completion Date :

Jul 15, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)