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

NCT00675714 | Terminated Phase 2 DMC

• 3 other identifiers: 04-157NIDILRR 90DP0043-03-00P50GM060338
• Study Type: interventional
• Target: 1,126
• Locations: 1 country
• Sites: 1

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.

Conditions

Burns

Keywords

anabolic agents; exercise

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (9)

1

EXPERIMENTAL

Humatrope subcutaneous(SQ) 0.05-0.2 mg/kg/day for up to 2 years post burn

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Drug: Humatrope

2

EXPERIMENTAL

Ketoconazole by mouth (PO) given twice a day throughout hospitalization for up to 2 years post burn

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Drug: Ketoconazole

3

EXPERIMENTAL

Oxandrolone PO given daily throughout hospitalization for up to 2 years post burn

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Drug: Oxandrolone

4

EXPERIMENTAL

Propranolol PO given daily throughout hospitalization for up to 2 years post burn

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Drug: Propranolol

5

EXPERIMENTAL

Oxandrolone and propranolol PO to be given daily for up to 2 years post burn

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Drug: Oxandrolone and propranolol combined

6

EXPERIMENTAL

Humatrope SQ and Propranolol PO to be given daily for up to 2 years post burn

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Drug: Humatrope and propranolol combined

7

PLACEBO COMPARATOR

Placebo PO to be given for up to 2 years post burn

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Drug: Placebo

8

EXPERIMENTAL

Exercise--hospital supervised intensive exercise program

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Behavioral: Exercise--Hospital supervised intensive exercise program

9

EXPERIMENTAL

Exercise--home or community based exercise program

Procedure: Stable Isotope Infusion Study; Procedure: Collection of blood and tissues; Procedure: Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI; Behavioral: Home exercise program

Interventions

Stable Isotope Infusion Study PROCEDURE

1-8 hour stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues.

1; 2; 3; 4; 5; 6; 7; 8; 9

Collection of blood and tissues PROCEDURE

Blood draw with each stable isotope infusion study and weekly Tissue biopsy: skin, fat, muscle at stable isotope infusion study

1; 2; 3; 4; 5; 6; 7; 8; 9

Radiology testing: Dual-energy X-ray absorptiometry (DEXA), ultrasound, MRI PROCEDURE

Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.

1; 2; 3; 4; 5; 6; 7; 8; 9

Humatrope DRUG

Humatrope (Growth Hormone) dose:0.05mg - 0.2mg/kg/day SQ daily for up to 2 years post burn injury.

Also known as: recombinant human growth hormone, Growth Hormone

1

Ketoconazole DRUG

Ketoconazole administration (or other glucocorticoid blocker--itraconazole or fluconazole) PO daily for up to 2 years post burn injury

Also known as: itraconazole, fluconazole

2

Oxandrolone DRUG

oxandrolone (or other anabolic steroid-testosterone or nandrolone) daily for up to 2 years post burn injury

Also known as: testosterone, nandrolone

3

Propranolol DRUG

Propranolol (or other beta adrenergic blocker--metoprolol, inderol), PO administration daily for up to 2 years post burn injury.

Also known as: metoprolol, inderol

4

Oxandrolone and propranolol combined DRUG

Daily administration of oxandrolone and propranolol to be given for up to 2 years post burn injury.

Also known as: testosterone, nandrolone, inderol, metoprolol

5

Humatrope and propranolol combined DRUG

Humatrope (growth hormone) and propranolol administration daily for up to 2 years post burn injury.

Also known as: recombinant human growth hormone, Growth Hormone, inderol, metoprolol

6

Placebo DRUG

placebo to be given once a day for up to two years post burn injury.

Also known as: control

7

Exercise--Hospital supervised intensive exercise program BEHAVIORAL

intensive exercise program supervised by trained personnel in the hospital environment for six up to twelve week program.

Also known as: exercise, intensive exercise, aerobic exercise, exercise rehabilitation program, hospital based exercise

8

Home exercise program BEHAVIORAL

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.

Also known as: Home exercise, intensive exercise, exercise rehabilitation

9

Eligibility Criteria

• Age: Up to 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Burn 30% Total Body Surface Area (TBSA) or greater
• Ages 0-80 yrs
• Negative pregnancy test
• Informed consent

You may not qualify if:

• 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)

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead
• U.S. Department of Education: collaborator
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Texas Medical Branch

Galveston, Texas, 77551, United States

Location

Related Publications (19)

• 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.

  PMID: 18243565 BACKGROUND

• 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.

  PMID: 28240622 DERIVED

• 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.

  PMID: 27433905 DERIVED

• Sousse LE, Herndon DN, Mlcak RP, Lee JO, Andersen CR, Zovath AJ, Finnerty CC, Suman OE. Long-Term Administration of Oxandrolone Improves Lung Function in Pediatric Burned Patients. J Burn Care Res. 2016 Sep-Oct;37(5):273-7. doi: 10.1097/BCR.0000000000000356.

  PMID: 27171844 DERIVED

• Diaz EC, Herndon DN, Lee J, Porter C, Cotter M, Suman OE, Sidossis LS, Borsheim 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.

  PMID: 25807408 DERIVED

• 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.

  PMID: 25514427 DERIVED

• 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.

  PMID: 25211297 DERIVED

• Chondronikola M, Meyer WJ, Sidossis LS, Ojeda S, Huddleston J, Stevens P, Borsheim 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.

  PMID: 24918945 DERIVED

• Hardee JP, Porter C, Sidossis LS, Borsheim 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.

  PMID: 24824900 DERIVED

• 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.

  PMID: 24655871 DERIVED

• Finnerty CC, Herndon DN. Is propranolol of benefit in pediatric burn patients? Adv Surg. 2013;47:177-97. doi: 10.1016/j.yasu.2013.02.001. No abstract available.

  PMID: 24298851 DERIVED

• 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.

  PMID: 24009246 DERIVED

• 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.

  PMID: 23303450 DERIVED

• 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.

  PMID: 23150682 DERIVED

• 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. doi: 10.1097/SLA.0b013e318265427e.

  PMID: 22895351 DERIVED

• 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.

  PMID: 22606232 DERIVED

• 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.

  PMID: 22463890 DERIVED

• Traber MG, Leonard SW, Traber DL, Traber LD, Gallagher J, Bobe G, Jeschke MG, Finnerty CC, Herndon D. alpha-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.

  PMID: 20881067 DERIVED

• 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.

  PMID: 19734776 DERIVED

Related Links

• University of Texas web page to describe funded program
• burn care web site includes information on funded grant project

MeSH Terms

Conditions

Burns; Motor Activity

Interventions

Absorptiometry, Photon; High-Energy Shock Waves; Magnetic Resonance Spectroscopy; Human Growth Hormone; Growth Hormone; Ketoconazole; Itraconazole; Fluconazole; Oxandrolone; Testosterone; Nandrolone; Propranolol; Metoprolol; Exercise; Exercise Therapy

Condition Hierarchy (Ancestors)

Wounds and Injuries; Behavior

Intervention Hierarchy (Ancestors)

Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena; Spectrum Analysis; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles; Azoles; Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Androstenols; Androstenes; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Estrenes; Estranes; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities

Study Officials

• David N Herndon, MD

  University of Texas

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: May 12, 2008
• Study Start: January 1, 2004
• Primary Completion: September 1, 2018
• Study Completion: July 15, 2019
• Last Updated: November 29, 2019

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)