Acute and Long-Term Outcome Investigations of Fenofibrate on Severely Burned Patients
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|ClinicalTrials.gov Identifier: NCT01574131|
Recruitment Status : Terminated (lost funding; Shriner Burn Hosp has revoked access to study records. No updates or results can be submitted)
First Posted : April 10, 2012
Last Update Posted : November 29, 2019
|Condition or disease||Intervention/treatment||Phase|
|Second or Third Degree Burns||Drug: Fenofibrate Drug: Sugar Pill||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Care Provider)|
|Official Title:||Acute and Long-Term Outcome Investigations of Fenofibrate on Severely Burned Patients|
|Study Start Date :||May 2012|
|Actual Primary Completion Date :||February 2016|
|Actual Study Completion Date :||February 2016|
Placebo Comparator: Sugar pill
Drug: Sugar Pill
pill every day for 6 months
Other Name: Placebo
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
- Mitochondrial fatty acid oxygenation [ Time Frame: 6 months post injury ]Changes in mitochondrial oxygen consumption, Palmitoyl-CoA, palmitoyl-L-Carnitine, Pyruvate, Malate, Malonyl-CoA
- Insulin sensitivity [ Time Frame: 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 [ Time Frame: 6 months post injury ]
- Glucose Metabolism [ Time Frame: 6 months post injury ]
- Amino Acid Metabolism [ Time Frame: 6 months post injury ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01574131
|United States, Texas|
|University of Texas Medical Branch|
|Galveston, Texas, United States, 77551|
|Principal Investigator:||David N Herndon, MD||University of Texas|