Glucose Control in Severely Burned Patients

Study Overview
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Brief Summary
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The central aim of this application is to determine whether improved outcomes with tight euglycemic control are due to insulin-specific responses. The investigators hypothesize that improving insulin resistance will lead to decreased inflammatory and hypermetabolic responses, as well as restored glucose metabolism, and so result in improved clinical outcome of severely burned patients.

Official Title
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Glucose Control in Severely Burned Patients: Mechanisms and Therapeutic Potential

Conditions
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Burns

Intervention / Treatment
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* Drug: Humulin R
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: between 18 and 90 years of age >20% TBSA Admitted to the burn unit within 120 hours following burn At least 1 surgical intervention necessary Exclusion Criteria: death upon admission decision not to treat due to burn injury severity presence of anoxic brain injury that is not expected to result in complete recovery known history of AIDS, ARC, HIV, Hepatitis B-E history of cancer within 5 years of malignancy currently under treatment inability to obtain informed consent previous or existing renal dysfunction, liver disease, or hepatic dysfunction pre-existing type I diabetes mellitus pregnancy allergy to metformin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br> | Drug: Metformin<br>* Metformin 850 mg q. 8 hours will be given to decrease blood glucose to 130-140 mg/dl.<br>|
| Experimental: Insulin<br> | Drug: Humulin R<br>* Humulin R (U-100) will be given i.v. The dose given will be adjusted in order to achieve a blood glucose level of 130-140 mg/dl.<br>|
| No Intervention: Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perform oral glucose tolerance test | Standard fasting oral glucose tolerance test with an intake of 75 g of glucose. Subsequent measurements (in mg/dl) of glucose in blood, insulin and c-peptide will be conducted over 2 hours. | at 1-2 months post-admission, up to 6 months | 
| Perform oral glucose tolerance test | Standard fasting oral glucose tolerance test with an intake of 75 g of glucose. Subsequent measurements (in mg/dl) of glucose in blood, insulin and c-peptide will be conducted over 2 hours. | assessed at discharge (1-4 months post admission depending on the severity of injury) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure concentrations of serum cytokines | Inflammatory response will be assessed by measuring the concentrations (in pg/ml)of a panel of serum cytokines (IL-1, IFN, TNF etc.) using the Bio-Plex 17-Plex Suspension assay. | weekly until discharge (1-4 months post admission depending on severity of injury) | 
| Record the episodes of sepsis | Patients will be assessed daily for episodes of sepsis. The total number of episodes over the course of hospital stay will be recorded. | daily until discharge (1-4 months post admission depending on severity of injury) | 
| Record the episodes of Pneumonia | Pneumonia is defined by new progressive and persistent infiltrate, consolidation or cavitations, inhalation injury based on chest X-ray. We will also follow the guidelines provided by the American Burn Association on the definition of Pneumonia in burn patients. Change in sputum (purulent or increased) will also be recorded. | daily until discharge (1-4 months post admission depending on severity of injury) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thermal injury, Chemical Burn, Flame Burn