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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	1100 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
Study Start Date :	January 2004
Estimated Primary Completion Date :	September 2018
Estimated Study Completion Date :	September 2018

Arms and Interventions

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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; 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), 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: 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), 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; 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), 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), 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

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Primary Outcome Measures :

1. 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 ]

Eligibility Criteria

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Ages Eligible for Study:	up to 80 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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, 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

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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 Medical Branch, Galveston

U.S. Department of Education

National Institutes of Health (NIH)

National Institute of General Medical Sciences (NIGMS)

Investigators

Study Director:	David N Herndon, MD	University of Texas

More Information

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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

University of Texas web page to describe funded program 

burn care web site includes information on funded grant project 

Publications:

Alloju SM, Herndon DN, McEntire SJ, Suman OE. Assessment of muscle function in severely burned children. Burns. 2008 Jun;34(4):452-9. doi: 10.1016/j.burns.2007.10.006. Epub 2008 Feb 20.

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

Guillory AN, Herndon DN, Silva MB 3rd, Andersen CR, Suman OE, Finnerty CC. Oxandrolone Coadministration Does Not Alter Plasma Propranolol Concentrations in Severely Burned Pediatric Patients. J Burn Care Res. 2017 Jul/Aug;38(4):243-250. doi: 10.1097/BCR.0000000000000494.

Herndon DN, Voigt CD, Capek KD, Wurzer P, Guillory A, Kline A, Andersen CR, Klein GL, Tompkins RG, Suman OE, Finnerty CC, Meyer WJ, Sousse LE. Reversal of Growth Arrest With the Combined Administration of Oxandrolone and Propranolol in Severely Burned Children. Ann Surg. 2016 Sep;264(3):421-8. doi: 10.1097/SLA.0000000000001844.

Diaz EC, Herndon DN, Lee J, Porter C, Cotter M, Suman OE, Sidossis LS, Børsheim E. Predictors of muscle protein synthesis after severe pediatric burns. J Trauma Acute Care Surg. 2015 Apr;78(4):816-22. doi: 10.1097/TA.0000000000000594.

Kraft R, Herndon DN, Finnerty CC, Cox RA, Song J, Jeschke MG. Predictive Value of IL-8 for Sepsis and Severe Infections After Burn Injury: A Clinical Study. Shock. 2015 Mar;43(3):222-7. doi: 10.1097/SHK.0000000000000294.

Patel P, Sallam HS, Ali A, Chandalia M, Suman O, Finnerty CC, Herndon DN, Abate N. Changes in fat distribution in children following severe burn injury. Metab Syndr Relat Disord. 2014 Dec;12(10):523-6. doi: 10.1089/met.2014.0098. Epub 2014 Sep 11.

Chondronikola M, Meyer WJ, Sidossis LS, Ojeda S, Huddleston J, Stevens P, Børsheim E, Suman OE, Finnerty CC, Herndon DN. Predictors of insulin resistance in pediatric burn injury survivors 24 to 36 months postburn. J Burn Care Res. 2014 Sep-Oct;35(5):409-15. doi: 10.1097/BCR.0000000000000017.

Hardee JP, Porter C, Sidossis LS, Børsheim E, Carson JA, Herndon DN, Suman OE. Early rehabilitative exercise training in the recovery from pediatric burn. Med Sci Sports Exerc. 2014 Sep;46(9):1710-6. doi: 10.1249/MSS.0000000000000296.

Finnerty CC, Ali A, McLean J, Benjamin N, Clayton RP, Andersen CR, Mlcak RP, Suman OE, Meyer W, Herndon DN. Impact of stress-induced diabetes on outcomes in severely burned children. J Am Coll Surg. 2014 Apr;218(4):783-95. doi: 10.1016/j.jamcollsurg.2014.01.038. Epub 2014 Jan 24.

Finnerty CC, Herndon DN. Is propranolol of benefit in pediatric burn patients? Adv Surg. 2013;47:177-97. Review.

Finnerty CC, Mabvuure NT, Ali A, Kozar RA, Herndon DN. The surgically induced stress response. JPEN J Parenter Enteral Nutr. 2013 Sep;37(5 Suppl):21S-9S. doi: 10.1177/0148607113496117.

Ray S, Ju X, Sun H, Finnerty CC, Herndon DN, Brasier AR. The IL-6 trans-signaling-STAT3 pathway mediates ECM and cellular proliferation in fibroblasts from hypertrophic scar. J Invest Dermatol. 2013 May;133(5):1212-20. doi: 10.1038/jid.2012.499. Epub 2013 Jan 10.

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. doi: 10.1371/journal.pone.0035465. 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. doi: 10.1016/j.jamcollsurg.2011.12.038.

Traber MG, Leonard SW, Traber DL, Traber LD, Gallagher J, Bobe G, Jeschke MG, Finnerty CC, Herndon D. α-Tocopherol adipose tissue stores are depleted after burn injury in pediatric patients. Am J Clin Nutr. 2010 Dec;92(6):1378-84. doi: 10.3945/ajcn.2010.30017. 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. doi: 10.1097/SLA.0b013e3181b8f9ca.

Responsible Party:	The University of Texas Medical Branch, Galveston
ClinicalTrials.gov Identifier:	NCT00675714 History of Changes
Other Study ID Numbers:	04-157; NIDILRR 90DP0043-03-00; P50GM060338 ( U.S. NIH Grant/Contract )
First Posted:	May 12, 2008
Last Update Posted:	May 31, 2017
Last Verified:	May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by The University of Texas Medical Branch, Galveston:

anabolic agents; exercise

Additional relevant MeSH terms:

Hormones; Testosterone; Methyltestosterone; Testosterone enanthate; Testosterone undecanoate; Testosterone 17 beta-cypionate; Oxandrolone; Nandrolone; Nandrolone decanoate; Nandrolone phenpropionate; Itraconazole; Ketoconazole; Fluconazole; Anabolic Agents; Propranolol

Metoprolol; Hydroxyitraconazole; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents