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

The University of Texas System (UT)

Status and phase

Terminated

Phase 3

Phase 2

Conditions

Hypermetabolism

Hyperglycemia

Insulin Resistance

Treatments

Drug: Metformin

Drug: Sugar pill

Study type

Interventional

Funder types

Other

Identifiers

NCT01666665

12-142

Details and patient eligibility

About

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.

Full 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.

Enrollment

36 patients

Sex

All

Ages

10 to 19 years old

Volunteers

No Healthy Volunteers

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