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

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.

Conditions

  • Insulin Resistance
  • Hypermetabolism
  • Hyperglycemia

Eligibility

Eligible Ages
Between 10 Years and 19 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2/Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
Single (Participant)

Arm Groups

ArmDescriptionAssigned Intervention
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
  • 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:
    • glucophage
Placebo Comparator
Sugar pill
sugar pill up to 3 times per day for 12 months
  • Drug: Sugar pill
    Sugar pill up to 3 times per day for 12 months
    Other names:
    • placebo

Recruiting Locations

Shriners Hospitals for Children
Galveston, Texas 77551
Contact:
Cathy Reed, BSN
409-770-6987
ca2reed@utmb.edu

More Details

NCT ID
NCT01666665
Status
Recruiting
Sponsor
The University of Texas Medical Branch, Galveston

Study Contact

Catherine Reed, RN, BSN
409-770-6987
ca2reed@utmb.edu

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.