Clinical trial NCT01666665: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Insulin Resistance
Hypermetabolism
Hyperglycemia
Keywords: Burn
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
Collaborators: name: Shriners Hospitals for Children
First posted: 2012-08-16
Enrollment: 36
Sex: ALL
Minimum age (years): 10
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Insulin resistance
timeFrame: Measure changes between admission and 2 years post burn
Secondary outcomes:
measure: Protein synthesis
timeFrame: Measure changes between admission and 1 years post burn
measure: Morbidity
timeFrame: Measure changes between admission and 2 years post burn
Other outcomes:
Locations:
city: Galveston
country: United States
facility: Shriners Hospitals for Children
state: Texas
Study officials:
affiliation: University of Texas
name: David N Herndon, MD
role: PRINCIPAL_INVESTIGATOR
References: