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

Second or Third Degree Burns Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01574131
• Other study ID #: 11-106
• Status: Terminated
• Phase: Phase 4
• Start date: May 2012
• Est. completion date: February 2016

Study information

• Verified date: February 2016
• Source: The University of Texas Medical Branch, Galveston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Second or Third Degree Burns

Intervention

Drug:
• Fenofibrate
Pill 54 mg or 160 mg tablets every day for 6 months Dosing-5mg/kg up to 160 mg for 6 months
• Sugar Pill
pill every day for 6 months

Locations

Country	Name	City	State
United States	University of Texas Medical Branch	Galveston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Medical Branch, Galveston	Shriners Hospitals for Children

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mitochondrial fatty acid oxygenation	Changes in mitochondrial oxygen consumption, Palmitoyl-CoA, palmitoyl-L-Carnitine, Pyruvate, Malate, Malonyl-CoA	6 months post injury
Secondary	Insulin sensitivity	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	6month post injury
Secondary	Protein Metabolism		6 months post injury
Secondary	Glucose Metabolism		6 months post injury
Secondary	Amino Acid Metabolism		6 months post injury