Mechanisms of Improved Wound Healing and Protein Synthesis of Insulin and Metformin | RxWiki

Mechanisms of Improved Wound Healing and Protein Synthesis of Insulin and Metformin

Overview[ - collapse ][ - ]

Purpose	Massive pediatric burns are associated with a persistent and sustained hypermetabolic response characterized by elevated levels of circulating catecholamine's, cortisol, and glucagon's, which can cause extreme muscle wasting, immunodeficiency, and delay in wound healing. Insulin and metformin have demonstrated anabolic activity with minimal associated side effects. However, it is unknown whether the beneficial effects arise from tight euglycemic control or direct effect of insulin action. We hypothesize that during acute hospitalization, administration of metformin at a dose titrated to maintain blood glucose between 80-180 mg/dl will accelerate wound healing and recovery in children with severe thermal injury and will have beneficial long-term effects on muscle strength, immune function, and wound healing.
Condition	Insulin Resistance Hypermetabolism Hyperglycemia
Intervention	Drug: Metformin Drug: Sugar pill
Phase	Phase 2/Phase 3
Sponsor	The University of Texas, Galveston
Responsible Party	The University of Texas, Galveston
ClinicalTrials.gov Identifier	NCT01666665
First Received	August 6, 2012
Last Updated	December 12, 2013
Last verified	December 2013

Tracking Information[ + expand ][ + ]

First Received Date	August 6, 2012
Last Updated Date	December 12, 2013
Start Date	November 2012
Estimated Primary Completion Date	August 2017
Current Primary Outcome Measures	Insulin resistance [Time Frame: Measure changes between admission and 2 years post burn] [Designated as safety issue: No]
Current Secondary Outcome Measures	Protein synthesis [Time Frame: Measure changes between admission and 2 years post burn] [Designated as safety issue: No] Morbidity [Time Frame: Measure changes between admission and 2 years post burn] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	Mechanisms of Improved Wound Healing and Protein Synthesis of Insulin and Metformin
Official Title	Mechanisms of Improved Wound Healing and Protein Synthesis of Insulin and Metformin
Brief Summary	Massive pediatric burns are associated with a persistent and sustained hypermetabolic response characterized by elevated levels of circulating catecholamine's, cortisol, and glucagon's, which can cause extreme muscle wasting, immunodeficiency, and delay in wound healing. Insulin and metformin have demonstrated anabolic activity with minimal associated side effects. However, it is unknown whether the beneficial effects arise from tight euglycemic control or direct effect of insulin action. We hypothesize that during acute hospitalization, administration of metformin at a dose titrated to maintain blood glucose between 80-180 mg/dl will accelerate wound healing and recovery in children with severe thermal injury and will have beneficial long-term effects on muscle strength, immune function, and wound healing.
Detailed Description	Metformin treated patients will be compared to control patients. Both groups will receive insulin therapy for blood glucose >180mg/dl. Insulin will be titrated according to hospital sliding scale. The use of insulin or metformin will benefit burned children by improving muscle protein build-up, speeding wound healing and reversing growth arrest, improving the immune response, and positively affecting long-term rehabilitation. The results of this study may initiate a change in standard of care as it is found that simply the reduction of blood glucose by metformin, improves patient outcomes as metformin can be administered without the added complication of hypoglycemia.
Study Type	Interventional
Study Phase	Phase 2/Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Insulin Resistance Hypermetabolism Hyperglycemia
Intervention	Drug: Metformin Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months Other Names: glucophageDrug: Sugar pill Sugar pill up to 3 times per day for 12 months Other Names: placebo
Study Arm (s)	Active Comparator: metformin Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months Placebo Comparator: Sugar pill sugar pill up to 3 times per day for 12 months

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	100
Estimated Completion Date	August 2017
Estimated Primary Completion Date	August 2017
Eligibility Criteria	Inclusion Criteria: - Patient age 10-19 - Primary diagnosis of ≥ 20 TBSAB (Total Burn Surface Area Burn) Exclusion Criteria: - Decision not to treat due to burn injury severity - Known history of AIDS, ARC, HIV - Pregnancy - persistent lactic acidosis - Previous existing renal failure, liver disease or hepatic dysfunction (Bilirubin >3mg/dL, SGOT >40u/L, GPT >51u/L serum Creatinine >3mg/dL after fluid resuscitation - Pre-existing type 1 diabetes mellitus - Allergies to Metformin
Gender	Both
Ages	10 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Catherine Reed, RN, BSN 409-770-6987 ca2reed@utmb.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01666665
Other Study ID Numbers	12-142
Has Data Monitoring Committee	Yes
Information Provided By	The University of Texas, Galveston
Study Sponsor	The University of Texas, Galveston
Collaborators	Shriners Hospitals for Children
Investigators	Principal Investigator: David N Herndon, MD University of Texas
Verification Date	December 2013

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