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Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients

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ClinicalTrials.gov Identifier: NCT03038594
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : January 9, 2018
Sponsor:
Collaborators:
United States Department of Defense
Pfizer
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

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, muscle protein synthesis and breakdown rates, quality of life questionnaires, and concentrations of relevant hormones, cytokines, and oxidative stress markers.

Condition or disease Intervention/treatment Phase
Burns Growth Hormone Treatment Drug: Somatropin Drug: 0.09% Saline Solution Phase 2 Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Growth Hormone Therapy for Muscle Regeneration in Severely Burned Patients
Study Start Date : November 2015
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Burns Hormones

Arm Intervention/treatment
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.
Drug: Somatropin
Other Name: Genotropin, Growth Hormone (GH)

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.
Drug: 0.09% Saline Solution
Other Name: Placebo, Control




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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

  7. 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

  8. Change in liver size [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Ultrasound readings

  9. 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

  10. Change in cardiac output [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Echocardiogram readings

  11. Change in respiratory quotient [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Indirect calorimetry

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 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

  17. 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

  18. 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

  19. Change in Muscle protein synthesis rate [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Stable-isotope, deuterium water, and doubly-labeled water study

  20. Change in Muscle protein breakdown rate [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Stable-isotope, deuterium water and doubly-labeled water study

  21. Hypertrophic scar development [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Vancouver Scar Scale

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. Changes in quality of life [ Time Frame: Discharge (usually 30 days post burn) and 6, 12, 18, and 24 months after burn injury ]
    Questionnaires



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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]

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03038594


Contacts
Contact: Ludwik K Branski, MD, MMS (832) 770 6741 lubransk@utmb.edu
Contact: Linda E Sousse, PhD, MBA (409) 770-6701 lesousse@utmb.edu

Locations
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77550-1220
Contact: Ludwik K Branski, MD, MMS         
Contact: Linda E Sousse, PhD, MBA         
Principal Investigator: Ludwik K Branski, MD, MMS         
Sub-Investigator: David N Herndon, MD         
Sub-Investigator: Celeste C Finnerty, PhD         
Sub-Investigator: Jong O Lee, MD         
Sub-Investigator: Linda E Sousse, PhD, MBA         
Sub-Investigator: Oscar E Suman, PhD         
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555-1220
Contact: Ludwik K Branski, MD, MMS    409-770-6589    lubransk@utmb.edu   
Contact: Linda E Sousse, PhD, MBA    (409) 770-6701    lesousse@utmb.edu   
Shriners Hospitals for Children-Galveston Recruiting
Galveston, Texas, United States, 77555
Contact: Ludwik K Branski, MD    409-770-6589    lubransk@utmb.edu   
Contact: Linda E Sousse, PhD, MBA    409-770-6701    lesousse@utmb.edu   
Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
United States Department of Defense
Pfizer
Investigators
Principal Investigator: Ludwik K Branski, MD, MMS University of Texas
Study Director: Linda E Sousse, PhD, MBA University of Texas

Publications:
Responsible Party: The University of Texas Medical Branch, Galveston
ClinicalTrials.gov Identifier: NCT03038594     History of Changes
Other Study ID Numbers: 15-0192
W81XWH-15-1-0143 ( Other Grant/Funding Number: US Department of Defense )
First Posted: January 31, 2017    Key Record Dates
Last Update Posted: January 9, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by The University of Texas Medical Branch, Galveston:
Burns
Growth Hormone
Lean Body Mass
Strength
Exercise Endurance

Additional relevant MeSH terms:
Pharmaceutical Solutions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs