Assessment of Mechanisms of Improved Wound Healing

Assessment of Mechanisms of Improved Wound Healing of Anabolic Agents and Diet in Severely Burned Patients

The purpose of this study is to find ways to improve wound healing and decrease the negative effects of trauma from burn injury.

Study Overview

• Status: Completed
• Conditions: Burns
• Intervention / Treatment: Procedure: Stable Isotope Infusion study; Drug: Growth Hormone; Drug: Insulin High Dose; Drug: oxandrolone; Drug: Propranolol; Drug: IGF-1/IGFBP-3; Drug: Insulin Low Dose; Drug: Itraconazole; Drug: Growth Hormone and Propranolol; Drug: Oxandrolone and Propranolol; Drug: Placebo or Control

Detailed Description

This study involves research and the investigators hope to learn the following: how or what effect one or more anabolic ("tissue building") agents have on muscle metabolism, wound healing, and immune function after severe burn. The agents include the following: growth hormone, insulin-like growth factor-1 in combination with its binding proteins, insulin, Beta-adrenergic blockers, Alpha Adrenergic Agonist, anabolic steroids such as testosterone, Oxandrolone and nandrolone, ketoconazole and its derivatives, dehydroepiandrosterone, fenofibrate, diet or the application of skin substitute.

• Study Type: Interventional
• Enrollment (Actual): 644
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77550
      • University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is between 0 and 90 years of age
• Patient 18 years and older consents to participate in study protocol. If patient is not able to consent, consent will be obtained from closest family member or legal guardian. Parental permission will be obtained for patients less than 18 years of age. Assent will be obtained from children 7-17 years of age if child is physically/mentally able to do so.
• greater than 30% TBSA burn requiring at least 1 operation with donor sites for skin grafting

Exclusion Criteria:

• Known history of AIDS, AIDS-related complex, Human Immunodeficiency Virus
• History of cancer within 5 years
• Tuberculosis, arthritis, cirrhosis, hyperlipidemia, bone or endocrine diseases, autoimmune diseases
• Chronic glucocorticoid or non-steroidal anti-inflammatory drug therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Growth Hormone; Growth Hormone administered daily until 95% wound healing. Stable Isotope Infusion Study with collection of blood and tissue	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: Growth Hormone; Recombinant Human Growth hormone to be administered daily until 95% wound healing.; Other Names: GH; rhGH; recombinant human Growth Hormone
Experimental: Insulin High Dose; Insulin IV administered continuously to 95% healing. Stable Isotope Infusion Study with collection of blood and tissue	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: Insulin High Dose; Insulin IV administered continuously throughout hospitalization until wounds are 95% healed.; Other Names: Regular Insulin
Experimental: Oxandrolone; Oxandrolone administered daily until 95% wound healing Stable Isotope Infusion Study with collection of blood and tissue	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: oxandrolone; Oxandrolone given daily throughout hospitalization until 95% wound healing.; Other Names: nandrolone
Experimental: Propranolol; Propranolol administered daily until 95% wound healing Stable Isotope Infusion Study with collection of blood and tissue	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: Propranolol; Propranolol to be given daily throughout hospitalization until 95% wound healing.
Experimental: IGF-1/IGFBP-3; IGF-1/IGFBP-3 will be administered until 95% wound healing	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: IGF-1/IGFBP-3; Insulin Like Growth Factor-1/Insulin like Growth Factor Binding Protein 3 administered until 95% wound healing; Other Names: Insulin Like Growth Factor
Experimental: Insulin Low Dose; Insulin Low Dose will be administered until 95% wound healing.	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: Insulin Low Dose; Insulin administered IV until 95% wound healing; Other Names: Insulin
Experimental: Itraconazole; Itraconazole will be administered until 95% wound healing.	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: Itraconazole; Itraconazole administered until 95% wound healing
Experimental: Growth Hormone and Propranolol; Growth Hormone and Propranolol will be administered until 95% wound healing.	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: Growth Hormone and Propranolol; Growth Hormone and Propranolol given until 95% wound healing; Other Names: GH and Propranolol
Experimental: Oxandrolone and Propranolol; Oxandrolone and Propranolol will be administered until 95% wound healing	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: Oxandrolone and Propranolol; Oxandrolone and Propranolol
Placebo Comparator: Control/Placebo; Placebo or Control will be administered until 95% wound healing	Procedure: Stable Isotope Infusion study; Stable isotope infusion study to be done following each surgery. Tagged isotopes to assess uptake into blood and tissues. Includes collection of blood and tissues (muscle); Drug: Placebo or Control; Administration of Placebo or Control until 95% wound healing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease Hypermetabolism as Measured by Stable Isotope Infusion Study	At the request of the study site, this study has been closed. Access to study-related data is unavailable, and the PI is no longer at the institution. Hence, we are unable to submit the results data. Although peer-reviewed articles have been located that reference NCT00673309, it is not clear and verifiable (without access to the actual study-related data) what the results for the study outcomes are.	Admission to burn unit to 95% wound healing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved Rate of Wound Healing	At the request of the study site, this study has been closed. Access to study-related data is unavailable, and the PI is no longer at the institution. Hence, we are unable to submit the results data. Although peer-reviewed articles have been located that reference NCT00673309, it is not clear and verifiable (without access to the actual study-related data) what the results for the study outcomes are.	Admission to burn unit to 95% wound healing
Incidence of Morbidity and Mortality	At the request of the study site, this study has been closed. Access to study-related data is unavailable, and the PI is no longer at the institution. Hence, we are unable to submit the results data. Although peer-reviewed articles have been located that reference NCT00673309, it is not clear and verifiable (without access to the actual study-related data) what the results for the study outcomes are.	Admission to burn unit to discharge
Incidence of Sepsis	At the request of the study site, this study has been closed. Access to study-related data is unavailable, and the PI is no longer at the institution. Hence, we are unable to submit the results data. Although peer-reviewed articles have been located that reference NCT00673309, it is not clear and verifiable (without access to the actual study-related data) what the results for the study outcomes are.	Admission to burn unit to 95% wound healing

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: David N. Herndon, MD, University of Texas

Publications and helpful links

General Publications

• Kraft R, Herndon DN, Finnerty CC, Shahrokhi S, Jeschke MG. Occurrence of multiorgan dysfunction in pediatric burn patients: incidence and clinical outcome. Ann Surg. 2014 Feb;259(2):381-7. doi: 10.1097/SLA.0b013e31828c4d04.
• 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.
• Jeschke MG, Gauglitz GG, Kulp GA, Finnerty CC, Williams FN, Kraft R, Suman OE, Mlcak RP, Herndon DN. Long-term persistance of the pathophysiologic response to severe burn injury. PLoS One. 2011;6(7):e21245. doi: 10.1371/journal.pone.0021245. Epub 2011 Jul 18.
• Jeschke MG, Kraft R, Emdad F, Kulp GA, Williams FN, Herndon DN. Glucose control in severely thermally injured pediatric patients: what glucose range should be the target? Ann Surg. 2010 Sep;252(3):521-7; discussion 527-8. doi: 10.1097/SLA.0b013e3181f2774c.
• Mecott GA, Herndon DN, Kulp GA, Brooks NC, Al-Mousawi AM, Kraft R, Rivero HG, Williams FN, Branski LK, Jeschke MG. The use of exenatide in severely burned pediatric patients. Crit Care. 2010;14(4):R153. doi: 10.1186/cc9222. Epub 2010 Aug 11.
• Jeschke MG, Kulp GA, Kraft R, Finnerty CC, Mlcak R, Lee JO, Herndon DN. Intensive insulin therapy in severely burned pediatric patients: a prospective randomized trial. Am J Respir Crit Care Med. 2010 Aug 1;182(3):351-9. doi: 10.1164/rccm.201002-0190OC. Epub 2010 Apr 15.
• Gauglitz GG, Herndon DN, Kulp GA, Meyer WJ 3rd, Jeschke MG. Abnormal insulin sensitivity persists up to three years in pediatric patients post-burn. J Clin Endocrinol Metab. 2009 May;94(5):1656-64. doi: 10.1210/jc.2008-1947. Epub 2009 Feb 24.
• Jeschke MG, Chinkes DL, Finnerty CC, Kulp G, Suman OE, Norbury WB, Branski LK, Gauglitz GG, Mlcak RP, Herndon DN. Pathophysiologic response to severe burn injury. Ann Surg. 2008 Sep;248(3):387-401. doi: 10.1097/SLA.0b013e3181856241.

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (Estimated): May 7, 2008

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: burns
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Androgens; Anabolic Agents; Insulin; Propranolol; Insulin, Globin Zinc; Hormones; Itraconazole; Nandrolone; Oxandrolone
• Other Study ID Numbers: 00-454; P50GM060338 (U.S. NIH Grant/Contract); R01GM056687 (U.S. NIH Grant/Contract); SHC #8660 (Other Grant/Funding Number: Shriners Hospital for children)