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Mitochondrial Oxidation and Insulin Resistance in Burn Patients Treated With Fenofibrate

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: NCT00732485
Recruitment Status : Withdrawn (Principal Investigator Changed)
First Posted : August 12, 2008
Last Update Posted : December 11, 2012
Shriners Hospitals for Children
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

Brief Summary:

Major burn injury causes significant insulin resistance on glucose and protein metabolism that persists for up to 6 months after the acute injury

This project proposes to answer the following questions:

  1. Will fenofibrate given to burn patients with insulin resistance restore their insulin sensitivity?
  2. What is the relationship between mitochondrial dysfunction in muscle tissue as the causative mechanism of burn related insulin resistance?
  3. To what extent will the restored insulin sensitivity affect glucose and protein metabolism in muscle, regenerating wounds and the liver, i.e. ameliorate burn related hyperglycemia and protein catabolism?

Condition or disease Intervention/treatment Phase
Burn Drug: fenofibrate Drug: placebo Phase 2 Phase 3

Detailed Description:

The following specific hypotheses will be investigated:

  1. Following severe burn injury in human patients the mitochondrial fat oxidation 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.
  2. Fatty acids, or their active intracellular products (e.g., DAG, acyl-CoenzymeA (Co-A), or acylcarnitine), are the direct inhibitors of insulin action, rather than tissue triglycerides (TG) itself. In other words, impaired mitochondrial fatty acid oxidation is the mechanism that causes altered lipid metabolism that ultimately contributes to insulin resistance.
  3. 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 acid (FFA) exceeding the rate of oxidation within muscle due principally to a reduced capacity of mitochondria to oxidize fatty acids.
  4. Decreased 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. We propose that increased tissue PKC activity will be associated with increased tissue concentration of DAG, acyl-CoA, or acylcarnitine.
  5. Treatment of patients with the peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate will improve mitochondrial capacity to oxidize fatty acids.
  6. 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 : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Role of Mitochondrial Oxidation on Insulin Resistance in Burn Patients Treated With Fenofibrate
Study Start Date : August 2008
Estimated Primary Completion Date : December 2012
Estimated Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Burns
Drug Information available for: Fenofibrate

Arm Intervention/treatment
Active Comparator: Fenofibrate Drug: fenofibrate
Fenofibrate, PO, 5 mg/kg/day from admission to 6 months post burn

Placebo Comparator: Placebo Drug: placebo
Placebo, sugar pill, from admission to 6 months post burn

Primary Outcome Measures :
  1. Insulin sensitivity on glucose and protein metabolism [ Time Frame: From admission to burn unit to 6 months post burn ]

Secondary Outcome Measures :
  1. Systemic glucose homeostasis [ Time Frame: Admission to 6 months post burn ]
  2. Muscle protein balance [ Time Frame: Admission to 6 months post burn ]
  3. Wound protein balance [ Time Frame: Admission to 6 months post burn ]

Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients > 7 years old with burns covering 40% or more of body surface who are admitted to the Shriners Hospital for Children, Galveston, Texas

Exclusion Criteria:

  • Abnormal liver and kidney function,
  • Pregnancy,
  • Diabetes mellitus,

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): NCT00732485

Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
Shriners Hospitals for Children
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Principal Investigator: David Herndon, MD University of Texas Medical Branch, Galveston
Publications of Results:
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Responsible Party: The University of Texas Medical Branch, Galveston Identifier: NCT00732485    
Other Study ID Numbers: 07-389
SHC 08-GAL-006
First Posted: August 12, 2008    Key Record Dates
Last Update Posted: December 11, 2012
Last Verified: December 2012
Keywords provided by The University of Texas Medical Branch, Galveston:
Burn injury
Insulin resistance
Mitochondrial function
Fat oxidation
Additional relevant MeSH terms:
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Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Wounds and Injuries
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents