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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Insulin Resistance, Hypermetabolism, Hyperglycemia

Intervention / Treatment
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* Drug: Metformin
* Drug: Sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient age 10-19 Primary diagnosis of ≥ 20 Total Burn Surface Area Burn (TBSAB ) Exclusion Criteria: Decision not to treat due to burn injury severity Known history of AIDS, ARC, HIV Pregnancy Previous diagnosis (pre -burn) of renal failure, liver disease or hepatic dysfunction- Serum Creatinine >1.5mg/dL for males and >1.4mg/dL for females, after fluid resuscitation (Clinical definition of kidney damage) Pre-existing type 1 diabetes mellitus Pre Existing type 2 diabetes mellitus and receiving treatment Allergies to Metformin Acute or chronic acidosis (lactic or any other metabolic type) and renal failure

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 19 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: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: metformin<br>Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months | Drug: Metformin<br>* Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months<br>* Other names: glucophage;|
| Placebo Comparator: Sugar pill<br>sugar pill up to 3 times per day for 12 months | Drug: Sugar pill<br>* Sugar pill up to 3 times per day for 12 months<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance | As measured by OGTT | Measure changes between admission and 2 years post burn | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protein synthesis | As measured by stable isotope infusion study | Measure changes between admission and 1 years post burn | 
| Morbidity | As measured by Organ Failure assessments | Measure changes between admission and 2 years post burn | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Burn