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

Purpose

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	Intervention	Phase
Burns	Procedure: Stable Isotope Infusion Study Procedure: Collection of blood and tissues Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), K+ counter, 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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Anabolic Steroids Burns Exercise and Physical Fitness Rehabilitation X-Rays

Drug Information available for: Oxandrolone Testosterone propionate Methyltestosterone Testosterone cypionate Testosterone Testosterone enanthate Propranolol hydrochloride Nandrolone decanoate Propranolol Somatropin Metoprolol Metoprolol tartrate Ketoconazole Itraconazole Fluconazole Metoprolol succinate Metoprolol fumarate

U.S. FDA Resources

Further study details as provided by The University of Texas, Galveston:

Primary Outcome Measures:

Outcome assessments will include measures of muscle wasting, weakness, immunosuppression chronic bone loss and decreased growth with increases in metabolic, hemodynamic, inflammatory and scarring responses. [ Time Frame: Admission to burn unit and up to 2 years post burn and yearly after that ] [ Designated as safety issue: No ]

Estimated Enrollment:	800
Study Start Date:	January 2004
Estimated Study Completion Date:	September 2017
Estimated Primary Completion Date:	September 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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), K+ counter, 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 GH rhGH 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), K+ counter, 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), K+ counter, 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), K+ counter, 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: metroprolol 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), K+ counter, 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), K+ counter, 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 GH rhGH inderol metoprolol growth hormone
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), K+ counter, 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 Name: 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), K+ counter, 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), K+ counter, 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

Detailed Description:

The University of Texas(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.

Eligibility

Ages Eligible for Study:	up to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Burn 30% Total Body Surface Area (TBSA) or greater
Ages 0-65 yrs
Negative pregnancy test
Informed consent

Exclusion Criteria:

Untreated malignancy, known history of AIDS, ARC, 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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00675714

Contacts

Contact: David N Herndon, MD	409-770-6731	dherndon@utmb.edu
Contact: Cathy L Reed, BSN	409-770-6987	ca2reed@utmb.edu

Locations

United States, Texas
University of Texas Medical Branch	Recruiting
Galveston, Texas, United States, 77551
Contact: David N Herndon, MD 409-770-6731 dherndon@utmb.edu
Contact: Cathy L Reed, BSN 409-770-6987 ca2reed@utmb.edu
Principal Investigator: David N Herndon, MD
Sub-Investigator: Oscar E Suman, PhD
Sub-Investigator: Celeste FInnerty, PhD

Sponsors and Collaborators

The University of Texas, Galveston

U.S. Department of Education

National Institutes of Health (NIH)

Shriners Hospitals for Children

Investigators

Study Director:

David N Herndon, MD

University of Texas

More Information

Additional Information:

University of Texas web page to describe funded program This link exits the ClinicalTrials.gov site

burn care web site includes information on funded grant project This link exits the ClinicalTrials.gov site

Publications:

Alloju SM, Herndon DN, McEntire SJ, Suman OE. Assessment of muscle function in severely burned children. Burns. 2008 Jun;34(4):452-9. Epub 2008 Feb 20.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kraft R, Herndon DN, Finnerty CC, Hiyama Y, Jeschke MG. Association of postburn fatty acids and triglycerides with clinical outcome in severely burned children. J Clin Endocrinol Metab. 2013 Jan;98(1):314-21. doi: 10.1210/jc.2012-2599. Epub 2012 Nov 12.

Herndon DN, Rodriguez NA, Diaz EC, Hegde S, Jennings K, Mlcak RP, Suri JS, Lee JO, Williams FN, Meyer W, Suman OE, Barrow RE, Jeschke MG, Finnerty CC. Long-term propranolol use in severely burned pediatric patients: a randomized controlled study. Ann Surg. 2012 Sep;256(3):402-11.

Jeschke MG, Williams FN, Finnerty CC, Rodriguez NA, Kulp GA, Ferrando A, Norbury WB, Suman OE, Kraft R, Branski LK, Al-mousawi AM, Herndon DN. The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes. PLoS One. 2012;7(5):e35465. Epub 2012 May 11.

Porro LJ, Herndon DN, Rodriguez NA, Jennings K, Klein GL, Mlcak RP, Meyer WJ, Lee JO, Suman OE, Finnerty CC. Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy. J Am Coll Surg. 2012 Apr;214(4):489-502; discussion 502-4.

Traber MG, Leonard SW, Traber DL, Traber LD, Gallagher J, Bobe G, Jeschke MG, Finnerty CC, Herndon D. ?-Tocopherol adipose tissue stores are depleted after burn injury in pediatric patients. Am J Clin Nutr. 2010 Dec;92(6):1378-84. Epub 2010 Sep 29.

Branski LK, Herndon DN, Barrow RE, Kulp GA, Klein GL, Suman OE, Przkora R, Meyer W 3rd, Huang T, Lee JO, Chinkes DL, Mlcak RP, Jeschke MG. Randomized controlled trial to determine the efficacy of long-term growth hormone treatment in severely burned children. Ann Surg. 2009 Oct;250(4):514-23.

Responsible Party:	The University of Texas, Galveston
ClinicalTrials.gov Identifier:	NCT00675714 History of Changes
Other Study ID Numbers:	04-157, NIDRR H133A020102, NIH P50 GM60338, SHC #8760
Study First Received:	December 26, 2007
Last Updated:	November 13, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by The University of Texas, Galveston:

anabolic agents
exercise

Additional relevant MeSH terms:

Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Nandrolone
Oxandrolone
Methyltestosterone
Hormones
Nandrolone decanoate
Nandrolone phenpropionate
Anabolic Agents
Metoprolol
Propranolol
Metoprolol succinate
Fluconazole

Ketoconazole
Itraconazole
Hydroxyitraconazole
Androgens
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents

ClinicalTrials.gov processed this record on May 23, 2013