Clinical trial NCT03038594: Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients
Official title: Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Burns
Growth Hormone Treatment
Keywords: Burns
Growth Hormone
Lean Body Mass
Strength
Exercise Endurance
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Pfizer
First posted: 2017-01-31
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Lean body mass
timeFrame: At baseline
measure: Lean body mass
timeFrame: 6 months post burn-injury
measure: Lean body mass
timeFrame: 12 months post burn-injury
measure: Lean body mass
timeFrame: 18 months post burn-injury
measure: Lean body mass
timeFrame: 24 months post burn-injury
Secondary outcomes:
measure: Change in Muscle strength (peak torque)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Muscle strength ( total work)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Muscle strength (average power)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Muscle grip strength (maximum power)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Muscle endurance (maximum power)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Resting energy expenditure (REE)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in resting heart rate
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in liver size
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in cardiac stroke volume
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in cardiac output
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in respiratory quotient
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Total body fat
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in percentage of total body fat
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in bone mineral content
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in bone mineral density
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Maximal oxygen consumption
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in respiratory fatigue
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in leg fatigue
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Muscle protein synthesis rate
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Hypertrophic scar development
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Forced vital capacity (FVC)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in forced expiratory volume in one second (FEV1)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in forced expiratory flow rate between 27-75% of the FVC (FEF25-75)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in FEV1/FVC ratio expressed as a percentage (FEV1/FVC%)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in vital capacity (VC)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in total lung capacity (TLC)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in residual volume (RV)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in functional residual capacity (FRC)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in lung diffusion capacity (DLCO)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in maximum voluntary ventilation (MVV)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in peak expiratory flow (PEF)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Change in Molecular biomarkers of oxidative and nitrosative stress (isoprostanes, asymmetric dimethylarginine)
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
measure: Changes in quality of life
timeFrame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury
Other outcomes:
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: University of Texas
name: Ludwik K Branski, MD, MMS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stylianos S, Eichelberger MR. Pediatric trauma. Prevention strategies. Pediatr Clin North Am. 1993 Dec;40(6):1359-68. doi: 10.1016/s0031-3955(16)38666-7.