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

Sponsor

The University of Texas Medical Branch, Galveston (Other)

Overall Status

Terminated

CT.gov ID

NCT01574131

Collaborator

Shriners Hospitals for Children (Other)

Enrollment

Location

Arms

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Second or Third Degree Burns	Drug: Fenofibrate Drug: Sugar Pill	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Feb 1, 2016

Actual Study Completion Date :

Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Sugar pill pill	Drug: Sugar Pill pill every day for 6 months Other Names: Placebo
Active Comparator: Fenofibrate ppar-alpha agonist	Drug: Fenofibrate Pill 54 mg or 160 mg tablets every day for 6 months Dosing-5mg/kg up to 160 mg for 6 months Other Names: Lofibra

Arm

Intervention/Treatment

Placebo Comparator: Sugar pill

pill

Drug: Sugar Pill

pill every day for 6 months

Other Names:

Placebo

Active Comparator: Fenofibrate

ppar-alpha agonist

Drug: Fenofibrate

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

Other Names:

Lofibra

Outcome Measures

Primary Outcome Measures

Mitochondrial fatty acid oxygenation [6 months post injury]
Changes in mitochondrial oxygen consumption, Palmitoyl-CoA, palmitoyl-L-Carnitine, Pyruvate, Malate, Malonyl-CoA

Secondary Outcome Measures

Insulin sensitivity [6month post injury]
Muscle amino acid uptake, protein synthesis and breakdown. Insulin receptor tyrosine kinase activity, insulin receptor substrate activity,protein kinase C activity,glucose uptake and enrichment. Fractioned synthetic rate of plasma proteins
Protein Metabolism [6 months post injury]
Glucose Metabolism [6 months post injury]
Amino Acid Metabolism [6 months post injury]

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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