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

Phase 2

Terminated

• Conditions: Insulin Resistance; Hypermetabolism; Hyperglycemia
• Interventions: Drug: Metformin; Drug: Sugar pill

• Registration Number: NCT01666665
• Lead Sponsor: The University of Texas Medical Branch, Galveston

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.

Study Timeline

• Study First Submitted: 2012-08-06
• Study First Submitted QC: 2012-08-10
• Study First Posted: 2012-08-16
• Study Start: 2012-11
• Status Verified: 2018-08
• Primary Completion: 2018-08
• Study Completion: 2019-04-23
• Last Update Submitted: 2019-11-26
• Last Update Posted: 2019-11-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Patient age 10-19
• Primary diagnosis of ≥ 20 Total Burn Surface Area Burn (TBSAB )

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
metformin	Metformin	Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months
Sugar pill	Sugar pill	sugar pill up to 3 times per day for 12 months

Primary Outcome Measures

Name	Time	Method
Insulin resistance	Measure changes between admission and 2 years post burn	As measured by OGTT

Secondary Outcome Measures

Name	Time	Method
Morbidity	Measure changes between admission and 2 years post burn	As measured by Organ Failure assessments
Protein synthesis	Measure changes between admission and 1 years post burn	As measured by stable isotope infusion study

Trial Locations

Locations (1)

Shriners Hospitals for Children; 🇺🇸 Galveston, Texas, United States