Acute and Long-Term Outcome Investigations of Fenofibrate on Severely Burned Patients

NCT ID: NCT01574131

Last Updated: 2019-11-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2016-02-29

Brief Summary

The purpose of this study is to learn the following: whether long-term treatment (6 months) with fenofibrate will decrease burn related sugar and fat increased in the blood and help prevent muscle loss and improve wound healing.

Detailed Description

Following severe burn injury in human patients the mitochondrial fat oxygenation capacity is decreased in muscle. This is associated with a corresponding progression in the severity of the resistance to the action of insulin on glucose disposal and protein synthesis and breakdown in muscle, regenerating wound and liver.

Fatty acids or their active intracellular products ( e.g. Diacylglycerol, acyl- Coenzyme A(CoA) or acylcarnitine) are the direct inhibitors of insulin action, rather than tissue triglycerides(TG) itself. In other words, impaired mitochondrial fatty acid oxygenation is the mechanism that causes altered lipid metabolism that ultimately contributes to insulin resistance.

Accumulation of active fatty acid products, such as Diacylglycerol, acyl-CoA or acylcarnitine esters in muscle cells is due to the rate of uptake of plasma free fatty acids(FFA) exceeding the rate of oxygenation within muscle due principally to a reduced capacity of mitochondria to oxidize fatty acids.

Decreasing insulin sensitivity in muscle is related to impaired insulin signaling. This will be reflected by increased activity of protein kinase C (PKC). Because PKC is thought to exert its regulatory effect primarily on either tyrosine kinase activity on the insulin receptor or downstream kinase insulin receptor substrate (IRS) phosphorylation, these elements of the insulin signaling cascade will be decreased. In turn, elements of insulin signaling related to the response of muscle glucose (PI3 Kinase) and protein (P70S6k)metabolism will be reduced. The investigators propose that increased tissue PKC activity will be associated with increased tissue concentration of Diacylglycerol, acyl-CoA or acylcarnitine. The investigators hypothesize that the treatment of patients with the peroxisome proliferator-activated receptor (PPAR) alpha antagonist fenofibrate will improve mitochondrial capacity to oxidize fatty acids. Insulin sensitivity in muscle, skin and liver in terms of both glucose and protein metabolism will be improved by fenofibrate treatment.

Conditions

Second or Third Degree Burns

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sugar pill

pill

Group Type: PLACEBO_COMPARATOR

Sugar Pill

Intervention Type: DRUG

pill every day for 6 months

Fenofibrate

ppar-alpha agonist

Group Type: ACTIVE_COMPARATOR

Fenofibrate

Intervention Type: DRUG

Pill 54 mg or 160 mg tablets every day for 6 months Dosing-5mg/kg up to 160 mg for 6 months

Interventions

Fenofibrate

Pill 54 mg or 160 mg tablets every day for 6 months Dosing-5mg/kg up to 160 mg for 6 months

Intervention Type: DRUG

Sugar Pill

pill every day for 6 months

Intervention Type: DRUG

Other Intervention Names

Lofibra; Placebo

Eligibility Criteria

Inclusion Criteria

• ≥40% Burn
• ages 4-20years
• body weight ≥10kg

Exclusion Criteria

• <40% burn
• ages <4->20 years
• body weight <10kg
• Respiratory insufficiency
• Multiple fractures
• History of cancer in last 5 years
• Bilirubin>3mg/dL
• Serum Creatinine>3mg/dL after fluid resuscitation
• Glutamyl-Oxaloacetic Transaminase(GOT) >40 Units/L
• Glutamyl-Pyruvate Transminase(GPT) >51 Units/L
• Associated head injuries requiring therapy
• Associated injuries to the chest or abdomen requiring surgery
• Receipt of any experimental drug other than the ones supplied within two months of study
• Any metal in body including rods, cardiac defibrillators, pacemaker, etc
• Orthopedic casting which would prevent placement in MRI
• Hepatitis
• Abnormal EKG
• Electrical burns

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 20 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

University of Texas Medical Branch

Galveston, Texas, United States

Countries

United States

Other Identifiers

11-106

Identifier Type: -

Identifier Source: org_study_id