Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients

Study Overview
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Brief Summary
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The investigators have previously demonstrated that burn injury causes severe muscle wasting, weight and height retardation, and systemic protein catabolism in pediatric and adult burned patients. The persistent loss of muscle impairs the quality of life of the burned patients, and it also delays autonomy and reintegration into the community. In 2009, the investigators showed that the daily injection of recombinant human growth hormone (GH) for nine months post discharge significantly increased height and weight, as well as lean body mass, in pediatric burned subjects. Our long-term goal is to improve the quality of life of burn patients by preventing height, weight, and muscle loss that may occur from severe protein catabolism. The objectives of this application are to a) attenuate height and weight in burned patients with the administration of GH, b) prevent or reverse loss of muscle and strength in these patients, and c) collect pilot data about cardiopulmonary parameters, scar assessments, and muscle metabolism. Our central hypothesis is that the administration of GH will restore depleted levels of growth hormone and will lead to prevention of lean body mass loss and bone mineral content, improve rehabilitation, and accelerate reintegration of severely burned patients. The investigators will administer either placebo or GH (daily subcutaneous injections of 0.05 mg/kg/day of GH [somatropin, Genotropin, Pfizer, New York, NY] to adult burn subjects (n=31 per group, 18-85 years, >30% total body surface burns) for nine months beginning one week prior to discharge. Both groups will be studied for a total of two years. The following aims will be tested: 1) determine the effects of GH supplementation on body composition, such as lean body mass loss, muscle strength, and exercise endurance; and 2) assess whether rehabilitation and subsequent reintegration of severely burned patients into society can be accelerated. Investigators will measure changes in lean body mass, muscle strength and exercise endurance during the acute hospital stay, discharge, and long-term follow-up visits (6, 12, 18, and 24 months after burn), as well as secondary endpoints such as cardiopulmonary variables, hypertrophic scar development, quality of life questionnaires, and concentrations of relevant hormones, cytokines, and oxidative stress markers.

Detailed Description
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Either recombinant human growth hormone (daily subcutaneous injections of 0.05 mg/kg/day of GH at discharge [somatropin, Genotropin, Pfizer, New York, NY]; 0.025 mg/kg/day of GH titrated the week before discharge) or placebo (n=31) will be administered to adult burned subjects (n= 31, 18-85 years) after screening and voluntary consent who have ≥30% TBSA assessed by either the Lund and Browder chart or the 'rule of nines' method during excisional surgery. It will be administered daily for 9 months beginning the week before discharge, and the primary and secondary endpoints will be collected during the acute hospital stay, discharge, and long-term follow-up visits (6, 12, 18, and 24 months after burn injury). Additionally, subjects will be contacted frequently [most likely 1 week, 1 month, and 2 months post discharge by telephone] to ensure that there are no adverse events or concerns with their study drug, as well as visit with them during their clinical visits that address their post-burn needs. All subjects will receive similar standard medical care and treatment from the time of emergency admission until their discharge. Growth hormone will be used to potentially attenuate losses in height, weight, muscle and bone, reverse the oxidative stress of burn injury and, in the process, decrease the secondary consequences of burn injury, including organ dysfunction. This may improve the quality of life of the burn patient by preventing pathophysiology that may result from muscle and bone loss and may reduce hospital stay. Our research will lay the foundation for the future development of effective, safe, and economic therapeutic interventions to treat burn injury-associated metabolic abnormalities. Also, it will provide the basis for the development of supplemental regulations and pharmacotherapy to treat burn patients with GH. The risks are very reasonable in relation to the anticipated benefits to our subjects because a) GH at a higher dose has been tested in pediatric burned subjects with minor adverse events, and b) the subjects will be monitored consistently.

Official Title
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Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients

Conditions
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Burns, Growth Hormone Treatment

Intervention / Treatment
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* Drug: Somatropin
* Drug: 0.09% Saline Solution


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA 18-85 years old Over 30% total body surface area burn Provide consent and comprehend English or Spanish EXCLUSION CRITERIA History of AIDS, AIDS-related complex, or HIV History of or current hepatitis B or C Pregnancy History of or Active Malignancy Insulin dependent diabetes mellitus type I prior to admission Insulin dependent diabetes mellitus type II (up to 12 months prior to admission) Other hyperglycemic disorders [not including transient post-burn/trauma hyperglycemia] Current oral corticosteroid treatment Currently participating in another interventional clinical trial at UTMB

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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>Daily subcutaneous injections of 0.05 mg/kg/day of Growth Hormone [somatropin, Genotropin, Pfizer, New York, NY] will be administered, from one week prior to discharge until 9 months post-burn. | Drug: Somatropin<br> <br> * Other names: Genotropin, Growth Hormone (GH);|
| Placebo Comparator: 0.09% saline solution<br>Daily subcutaneous injections of 0.09% of saline solution will be administered, from one week prior to discharge until 9 months post-burn. | Drug: 0.09% Saline Solution<br> <br> * Other names: Placebo, Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lean body mass | Dual-Energy X-ray Absorptiometry (DEXA) measured in grams | At baseline | 
| Lean body mass | Dual-Energy X-ray Absorptiometry (DEXA) measured in grams | 6 months post burn-injury | 
| Lean body mass | Dual-Energy X-ray Absorptiometry (DEXA) measured in grams | 12 months post burn-injury | 
| Lean body mass | Dual-Energy X-ray Absorptiometry (DEXA) measured in grams | 18 months post burn-injury | 
| Lean body mass | Dual-Energy X-ray Absorptiometry (DEXA) measured in grams | 24 months post burn-injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Muscle strength (peak torque) | resistance testing muscle strength (assessed by Biodex isokinetic dynamometer) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Muscle strength ( total work) | resistance testing muscle strength (Biodex isokinetic dynamometer) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Muscle strength (average power) | resistance testing muscle strength (assessed by Biodex isokinetic dynamometer) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Muscle grip strength (maximum power) | testing muscle strength (assessed by hand dynamometer) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Muscle endurance (maximum power) | testing muscle endurance (assessed by Bruce treadmill test) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Resting energy expenditure (REE) | Indirect calorimetry | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in resting heart rate | electrocardiogram (EKG) readings | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in liver size | Ultrasound readings | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in cardiac stroke volume | echocardiogram readings | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in cardiac output | Echocardiogram readings | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in respiratory quotient | Indirect calorimetry | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Total body fat | Dual-Energy X-ray Absorptiometry (DEXA) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in percentage of total body fat | Dual-Energy X-ray Absorptiometry (DEXA) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in bone mineral content | Dual-Energy X-ray Absorptiometry (DEXA) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in bone mineral density | Dual-Energy X-ray Absorptiometry (DEXA) | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Maximal oxygen consumption | Six-minute walk test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in respiratory fatigue | Six-minute walk test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in leg fatigue | Six-minute walk test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Muscle protein synthesis rate | Deuterium water | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Hypertrophic scar development | Vancouver Scar Scale | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Forced vital capacity (FVC) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in forced expiratory volume in one second (FEV1) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in forced expiratory flow rate between 27-75% of the FVC (FEF25-75) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in FEV1/FVC ratio expressed as a percentage (FEV1/FVC%) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in vital capacity (VC) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in total lung capacity (TLC) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in residual volume (RV) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in functional residual capacity (FRC) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in lung diffusion capacity (DLCO) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in maximum voluntary ventilation (MVV) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in peak expiratory flow (PEF) | Pulmonary function test | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Change in Molecular biomarkers of oxidative and nitrosative stress (isoprostanes, asymmetric dimethylarginine) | Urine analysis | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 
| Changes in quality of life | Questionnaires | Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Burns, Growth Hormone, Lean Body Mass, Strength, Exercise Endurance