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Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients

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ClinicalTrials.gov Identifier: NCT03038594
Recruitment Status : Active, not recruiting
First Posted : January 31, 2017
Last Update Posted : January 18, 2019
Sponsor:
Collaborators:
United States Department of Defense
Pfizer
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

Tracking Information
First Submitted Date  ICMJE May 11, 2016
First Posted Date  ICMJE January 31, 2017
Last Update Posted Date January 18, 2019
Actual Study Start Date  ICMJE November 2015
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2018)
Change in Lean body mass [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
Dual-Energy X-ray Absorptiometry (DEXA)
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2017)
Change in Lean body mass [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
Dual-Energy X-ray Absorptiometry (DEXA)
Change History Complete list of historical versions of study NCT03038594 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2019)
  • Change in Muscle strength (peak torque) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    resistance testing muscle strength (assessed by Biodex isokinetic dynamometer)
  • Change in Muscle strength ( total work) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    resistance testing muscle strength (Biodex isokinetic dynamometer)
  • Change in Muscle strength (average power) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    resistance testing muscle strength (assessed by Biodex isokinetic dynamometer)
  • Change in Muscle grip strength (maximum power) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    testing muscle strength (assessed by hand dynamometer)
  • Change in Muscle endurance (maximum power) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    testing muscle endurance (assessed by Bruce treadmill test)
  • Change in Resting energy expenditure (REE) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Indirect calorimetry
  • Change in resting heart rate [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    electrocardiogram (EKG) readings
  • Change in liver size [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Ultrasound readings
  • Change in cardiac stroke volume [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    echocardiogram readings
  • Change in cardiac output [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Echocardiogram readings
  • Change in respiratory quotient [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Indirect calorimetry
  • Change in Total body fat [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Dual-Energy X-ray Absorptiometry (DEXA)
  • Change in percentage of total body fat [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Dual-Energy X-ray Absorptiometry (DEXA)
  • Change in bone mineral content [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Dual-Energy X-ray Absorptiometry (DEXA)
  • Change in bone mineral density [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Dual-Energy X-ray Absorptiometry (DEXA)
  • Change in Maximal oxygen consumption [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Six-minute walk test
  • Change in respiratory fatigue [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Six-minute walk test
  • Change in leg fatigue [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Six-minute walk test
  • Change in Muscle protein synthesis rate [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Deuterium water
  • Hypertrophic scar development [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Vancouver Scar Scale
  • Changes in donor site healing time [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Laser Doppler measurements
  • Change in Forced vital capacity (FVC) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in forced expiratory volume in one second (FEV1) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in forced expiratory flow rate between 27-75% of the FVC (FEF25-75) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in FEV1/FVC ratio expressed as a percentage (FEV1/FVC%) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in vital capacity (VC) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in total lung capacity (TLC) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in residual volume (RV) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in functional residual capacity (FRC) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in lung diffusion capacity (DLCO) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in maximum voluntary ventilation (MVV) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in peak expiratory flow (PEF) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Pulmonary function test
  • Change in Molecular collagen formation [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Biopsy of burned and unburned skin
  • Change in Molecular biomarkers of oxidative and nitrosative stress (isoprostanes, asymmetric dimethylarginine) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Urine analysis
  • Changes in quality of life [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Questionnaires
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2017)
  • Change in Muscle strength (peak torque) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    resistance testing muscle strength (assessed by Biodex isokinetic dynamometer)
  • Change in Muscle strength ( total work) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    resistance testing muscle strength (Biodex isokinetic dynamometer)
  • Change in Muscle strength (average power) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    resistance testing muscle strength (assessed by Biodex isokinetic dynamometer)
  • Change in Muscle grip strength (maximum power) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    testing muscle strength (assessed by hand dynamometer)
  • Change in Muscle endurance (maximum power) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    testing muscle endurance (assessed by Bruce treadmill test)
  • Change in Resting energy expenditure (REE) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Indirect calorimetry
  • Change in resting heart rate [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    electrocardiogram (EKG) readings
  • Change in liver size [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Ultrasound readings
  • Change in cardiac stroke volume [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    echocardiogram readings
  • Change in cardiac output [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Echocardiogram readings
  • Change in respiratory quotient [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Indirect calorimetry
  • Change in Total body fat [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Dual-Energy X-ray Absorptiometry (DEXA)
  • Change in percentage of total body fat [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Dual-Energy X-ray Absorptiometry (DEXA)
  • Change in bone mineral content [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Dual-Energy X-ray Absorptiometry (DEXA)
  • Change in bone mineral density [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Dual-Energy X-ray Absorptiometry (DEXA)
  • Change in Maximal oxygen consumption [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Six-minute walk test
  • Change in respiratory fatigue [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Six-minute walk test
  • Change in leg fatigue [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Six-minute walk test
  • Change in Muscle protein synthesis rate [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Stable-isotope, deuterium water, and doubly-labeled water study
  • Change in Muscle protein breakdown rate [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Stable-isotope, deuterium water and doubly-labeled water study
  • Hypertrophic scar development [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Vancouver Scar Scale
  • Changes in donor site healing time [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Laser Doppler measurements
  • Change in Forced vital capacity (FVC) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in forced expiratory volume in one second (FEV1) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in forced expiratory flow rate between 27-75% of the FVC (FEF25-75) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in FEV1/FVC ratio expressed as a percentage (FEV1/FVC%) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in vital capacity (VC) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in total lung capacity (TLC) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in residual volume (RV) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in functional residual capacity (FRC) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in lung diffusion capacity (DLCO) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in maximum voluntary ventilation (MVV) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in peak expiratory flow (PEF) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Pulmonary function test
  • Change in Molecular collagen formation [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Biopsy of burned and unburned skin
  • Change in Molecular biomarkers of oxidative and nitrosative stress (isoprostanes, asymmetric dimethylarginine) [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after discharge ]
    Urine analysis
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients
Official Title  ICMJE Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Burns
  • Growth Hormone Treatment
Intervention  ICMJE
  • Drug: Somatropin
    Other Name: Genotropin, Growth Hormone (GH)
  • Drug: 0.09% Saline Solution
    Other Name: Placebo, Control
Study Arms  ICMJE
  • Experimental: Growth Hormone
    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.
    Intervention: Drug: Somatropin
  • Placebo Comparator: 0.09% saline solution
    Daily subcutaneous injections of 0.09% of saline solution will be administered, from one week prior to discharge until 9 months post-burn.
    Intervention: Drug: 0.09% Saline Solution
Publications * Stylianos S, Eichelberger MR. Pediatric trauma. Prevention strategies. Pediatr Clin North Am. 1993 Dec;40(6):1359-68.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: January 28, 2017)
62
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA

  • 18-85 years old
  • Over 30% total body surface area burn

EXCLUSION CRITERIA

  • History of AIDS, AIDS-related complex, or HIV
  • History of hepatitis
  • Pregnancy
  • History of or Active Malignancy
  • History of Insulin Dependent Diabetes Mellitus Type I or II
  • Other hyperglycemic disorders [not including transient post-burn/trauma hyperglycemia]
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03038594
Other Study ID Numbers  ICMJE 15-0192
W81XWH-15-1-0143 ( Other Grant/Funding Number: US Department of Defense )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party The University of Texas Medical Branch, Galveston
Study Sponsor  ICMJE The University of Texas Medical Branch, Galveston
Collaborators  ICMJE
  • United States Department of Defense
  • Pfizer
Investigators  ICMJE
Principal Investigator: Ludwik K Branski, MD, MMS University of Texas
Study Director: Linda E Sousse, PhD, MBA University of Texas
PRS Account The University of Texas Medical Branch, Galveston
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP