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

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.

Study Overview

• Status: Terminated
• Conditions: Hyperglycemia; Insulin Resistance; Hypermetabolism
• Intervention / Treatment: Drug: Metformin; Drug: Sugar pill

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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77551
      • Shriners Hospitals for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	As measured by OGTT	Measure changes between admission and 2 years post burn

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Collaborators: Shriners Hospitals for Children

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): April 23, 2019

Study Registration Dates

• First Submitted: August 6, 2012
• First Submitted That Met QC Criteria: August 10, 2012
• First Posted (Estimate): August 16, 2012

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Burn
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Hyperglycemia; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 12-142

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO