Acute and Long-Term Outcome Investigations of Fenofibrate on Severely Burned Patients
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|Official Title:||Acute and Long-Term Outcome Investigations of Fenofibrate on Severely Burned Patients|
- Mitochondrial fatty acid oxygenation [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]Changes in mitochondrial oxygen consumption, Palmitoyl-CoA, palmitoyl-L-Carnitine, Pyruvate, Malate, Malonyl-CoA
- Insulin sensitivity [ Time Frame: 6month post injury ] [ Designated as safety issue: No ]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 [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
- Glucose Metabolism [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
- Amino Acid Metabolism [ Time Frame: 6 months post injury ] [ Designated as safety issue: No ]
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Placebo Comparator: Sugar pill
pill every day for 6 months
Other Name: sugar pill
Active Comparator: Fenofibrate
Pill 54 mg or 160 mg tablets every day for 6 months Dosing-5mg/kg up to 160 mg for 6 months
Other Name: Lofibra
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. DAG, 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 DAG, 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 DAG, 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01574131
|Contact: Deb Benjamin, MSNfirstname.lastname@example.org|
|Contact: Cathy L Reed, BSNemail@example.com|
|United States, Texas|
|University of Texas Medical Branch||Recruiting|
|Galveston, Texas, United States, 77551|
|Contact: Deb Benjamin, MSN 409-770-6731 firstname.lastname@example.org|
|Contact: Cathy L Reed, BSN 409-770-6987 email@example.com|
|Principal Investigator: David N Herndon, MD|
|Principal Investigator:||David N Herndon, MD||University of Texas|