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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. 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
Shriners Hospitals for Children
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

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.

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Study Type : Interventional  (Clinical Trial)
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 2012
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Burns
Drug Information available for: Fenofibrate

Arm Intervention/treatment
Placebo Comparator: Sugar pill
Drug: Sugar Pill
pill every day for 6 months
Other Name: 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 Name: Lofibra

Primary Outcome Measures :
  1. Mitochondrial fatty acid oxygenation [ Time Frame: 6 months post injury ]
    Changes in mitochondrial oxygen consumption, Palmitoyl-CoA, palmitoyl-L-Carnitine, Pyruvate, Malate, Malonyl-CoA

Secondary Outcome Measures :
  1. 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

  2. Protein Metabolism [ Time Frame: 6 months post injury ]
  3. Glucose Metabolism [ Time Frame: 6 months post injury ]
  4. Amino Acid Metabolism [ Time Frame: 6 months post injury ]

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01574131

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United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77551
Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
Shriners Hospitals for Children
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Principal Investigator: David N Herndon, MD University of Texas
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Responsible Party: The University of Texas Medical Branch, Galveston Identifier: NCT01574131    
Other Study ID Numbers: 11-106
First Posted: April 10, 2012    Key Record Dates
Last Update Posted: November 29, 2019
Last Verified: February 2016
Keywords provided by The University of Texas Medical Branch, Galveston:
PPAR alpha agonist
insulin sensitivity
Additional relevant MeSH terms:
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Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents