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

NCT01666665 | Terminated Phase 2 DMC

• 1 other identifier: 12-142
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Insulin Resistance; Hypermetabolism; Hyperglycemia

Keywords

Burn

Outcome Measures

Primary Outcomes (1)

• Insulin resistance

  As measured by OGTT

  Measure changes between admission and 2 years post burn

Secondary Outcomes (2)

• Protein synthesis

  Measure changes between admission and 1 years post burn

• Morbidity

  Measure changes between admission and 2 years post burn

Study Arms (2)

metformin

ACTIVE COMPARATOR

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

Drug: Metformin

Sugar pill

PLACEBO COMPARATOR

sugar pill up to 3 times per day for 12 months

Drug: Sugar pill

Interventions

Metformin DRUG

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

Also known as: glucophage

metformin

Sugar pill DRUG

Sugar pill up to 3 times per day for 12 months

Also known as: placebo

Sugar pill

Eligibility Criteria

• Age: 10 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead
• Shriners Hospitals for Children: collaborator

Study Sites (1)

Shriners Hospitals for Children

Galveston, Texas, 77551, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Hyperglycemia; Burns

Interventions

Metformin; Sugars

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Carbohydrates

Study Officials

• David N Herndon, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2012
• First Posted: August 16, 2012
• Study Start: November 1, 2012
• Primary Completion: August 1, 2018
• Study Completion: April 23, 2019
• Last Updated: November 29, 2019

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)