Official Title: “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 Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2010

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.

Intervention(s) in this Clinical Trial

• 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: 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: Radiology testing: DEXA, K+ counter, ultrasound, MRI
  • Testing to be done following every stable isotope infusion study to measure muscle, fat and bone tissues.
• Drug: IGF-1
  • Administration of randomized drug daily throughout hospitalization to 95% wound healing
• Drug: Insulin
  • Insulin IV administered continuously to maintain serum glucose between 80-110 throughout hospitalization until wounds are 95% healed.
• Drug: oxandrolone
  • Oxandrolone given daily throughout hospitalization until 95% wound healing.
• Drug: Propranolol
  • Propranolol to be given daily to decrease HR and BP throughout hospitalization until 95% wound healing.
• Drug: Clonidine
  • Clonidine administered daily throughout hospitalization until 95% wound healing to decrease HR, BP, and anxiety.
• Drug: Ketoconazole
  • Ketoconazole administered PO every 12 hours throughout hospitalization until 95% wound healing.
• Drug: Dehydroepiandrosterone-sulfate
  • The hormone Dehydroepiandrosterone-sulfate will be given daily until 95% wound healing.
• Drug: Fenofibrate
  • Fenofibrate administered daily until 95% wound healing.
• Drug: Metformin
  • metformin to be administered daily throughout hospitalization until 95% wound healing.
• Drug: Byetta
  • Byetta administered daily throughout hospitalization until 95% wound healing.
• Drug: Growth Hormone
  • Recombinant Human Growth hormone to be administered daily until 95% wound healing.
• Drug: Pioglitazone
  • Pioglitazone administered daily throughout hospitalization until 95% wound healing

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Growth Hormone 0.05 to 0.2 mg/kg q day SQ until 95% wound healing.
• Experimental: 2
  • IGF-1 (or IGF-1/IGFBP-3) administration daily until 95% wound healing
• Experimental: 3
  • Insulin IV administered continuously to maintain serum glucose between 80-110 throughout hospitalization until wounds are 95% healed
• Experimental: 4
  • Oxandrolone (or other Anabolic steroid-nandrolone or testosterone) administered daily until 95% wound healing
• Experimental: 5
  • Propranolol (or other Beta adrenergic blockers-metoprolol) to be given IV or PO to decrease HR and BP throughout hospitalization until 95% wound healing
• Experimental: 6
  • Clonidine (Alpha Adrenergic Agonist) to be given daily to decrease HR and BP and anxiety
• Experimental: 7
  • Ketoconazole (or other glucocorticoid blockers- itraconazole, fluconazole) administered PO every 12 hours throughout hospitalization until 95% wound healing
• Experimental: 8
  • Fenofibrate administered daily until 95% wound healing
• Experimental: 10
  • Pioglitazone administered daily throughout hospitalization to 95% wound healing
• Experimental: 11
  • Byetta (or other Glucagon like peptide drug-GLP, GLP-1, Exenatide) will be administered SQ daily throughout hospitalization until 95% wound healing
• Placebo Comparator: 12
  • Placebo. Sterile water will be administered daily throughout hospitalization to 95% wound healing
• Experimental: 9
  • Metformin PO administered daily throughout hospitalization to 95% wound healing
• Experimental: 13
  • DHEA-S, Dehydroepiandrosterone-sulfate administered daily until 95% wound healing.

Primary Measures

• Decrease hypermetabolism as measured by stable isotope infusion study
  • Time Frame: Admission to burn unit to 95% wound healing
    Safety Issue?: No

Secondary Measures

• Improved rate of wound healing
  • Time Frame: Admission to burn unit to 95% wound healing
    Safety Issue?: No
• Incidence of morbidity and mortality
  • Time Frame: Admission to burn unit to discharge
    Safety Issue?: No
• Incidence of sepsis
  • Time Frame: Admission to burn unit to 95% wound healing
    Safety Issue?: No

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 2 operations 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: The University of Texas, Galveston

Overall Clinical Trial Officials and Contacts

David N. Herndon, MD Principal Investigator University of Texas  

Overall Contact: David N. Herndon, MD 409-770-6733 dherndon@utmb.edu

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00673309

Study ID Number: 00-454

ClinicalTrials.gov Identifier: NCT00673309

Health Authority: United States: Institutional Review Board