Assessment of Mechanisms of Improved Wound Healing

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

Detailed Description
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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.

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

Conditions
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Burns

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Growth Hormone<br>Growth Hormone administered daily until 95% wound healing. Stable Isotope Infusion Study with collection of blood and tissue | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: Growth Hormone<br>* Recombinant Human Growth hormone to be administered daily until 95% wound healing.<br>* Other names: recombinant human Growth Hormone;|
| Experimental: Insulin High Dose<br>Insulin IV administered continuously to 95% healing. Stable Isotope Infusion Study with collection of blood and tissue | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: Insulin High Dose<br>* Insulin IV administered continuously throughout hospitalization until wounds are 95% healed.<br>* Other names: Regular Insulin;|
| Experimental: Oxandrolone<br>Oxandrolone administered daily until 95% wound healing Stable Isotope Infusion Study with collection of blood and tissue | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: oxandrolone<br>* Oxandrolone given daily throughout hospitalization until 95% wound healing.<br>* Other names: nandrolone;|
| Experimental: Propranolol<br>Propranolol administered daily until 95% wound healing Stable Isotope Infusion Study with collection of blood and tissue | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: Propranolol<br>* Propranolol to be given daily throughout hospitalization until 95% wound healing.<br>|
| Experimental: IGF-1/IGFBP-3<br>IGF-1/IGFBP-3 will be administered until 95% wound healing | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: IGF-1/IGFBP-3<br>* Insulin Like Growth Factor-1/Insulin like Growth Factor Binding Protein 3 administered until 95% wound healing<br>* Other names: Insulin Like Growth Factor;|
| Experimental: Insulin Low Dose<br>Insulin Low Dose will be administered until 95% wound healing. | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: Insulin Low Dose<br>* Insulin administered IV until 95% wound healing<br>* Other names: Insulin;|
| Experimental: Itraconazole<br>Itraconazole will be administered until 95% wound healing. | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: Itraconazole<br>* Itraconazole administered until 95% wound healing<br>|
| Experimental: Growth Hormone and Propranolol<br>Growth Hormone and Propranolol will be administered until 95% wound healing. | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: Growth Hormone and Propranolol<br>* Growth Hormone and Propranolol given until 95% wound healing<br>* Other names: GH and Propranolol;|
| Experimental: Oxandrolone and Propranolol<br>Oxandrolone and Propranolol will be administered until 95% wound healing | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: Oxandrolone and Propranolol<br>* Oxandrolone and Propranolol<br>|
| Placebo Comparator: Control/Placebo<br>Placebo or Control will be administered until 95% wound healing | Procedure: Stable Isotope Infusion study<br>* 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)<br>Drug: Placebo or Control<br>* Administration of Placebo or Control until 95% wound healing<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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burns