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

NCT ID: NCT01666665

Last Updated: 2019-11-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2019-04-23

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.

Conditions

Insulin Resistance; Hypermetabolism; Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

metformin

Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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 up to 3 times per day for 12 months

Group Type: PLACEBO_COMPARATOR

Sugar pill

Intervention Type: DRUG

Sugar pill up to 3 times per day for 12 months

Interventions

Metformin

Metformin up to 1000mg/m2 body surface area by mouth of feeding tube up to 3 times each day for 12 months

Intervention Type: DRUG

Sugar pill

Sugar pill up to 3 times per day for 12 months

Intervention Type: DRUG

Other Intervention Names

glucophage; placebo

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shriners Hospitals for Children

OTHER

Sponsor Role: collaborator

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David N Herndon, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Locations

Shriners Hospitals for Children

Galveston, Texas, United States

Countries

United States

Other Identifiers

12-142

Identifier Type: -

Identifier Source: org_study_id