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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by The University of Texas Medical Branch, Galveston
Shriners Hospitals for Children
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston Identifier:
First received: March 22, 2012
Last updated: June 11, 2015
Last verified: June 2015

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 Intervention Phase
Second or Third Degree Burns
Drug: Fenofibrate
Drug: placebo
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by The University of Texas Medical Branch, Galveston:

Primary Outcome Measures:
  • 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

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 40
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)
Arms Assigned Interventions
Placebo Comparator: Sugar pill
Drug: placebo
pill every day for 6 months
Other Name: sugar pill
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

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. 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.


Ages Eligible for Study:   4 Years to 20 Years
Genders Eligible for Study:   Both
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, neurofibrilators, pacemaker, etc
  • Orthopedic casting which would prevent placement in MRI
  • Hepatitis
  • Abnormal EKG
  • Electrical burns
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01574131

Contact: Deb Benjamin, MSN 409-770-6731
Contact: Cathy L Reed, BSN 409-770-6987

United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77551
Contact: Deb Benjamin, MSN    409-770-6731   
Contact: Cathy L Reed, BSN    409-770-6987   
Principal Investigator: David N Herndon, MD         
Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
Shriners Hospitals for Children
Principal Investigator: David N Herndon, MD University of Texas
  More Information

No publications provided

Responsible Party: The University of Texas Medical Branch, Galveston Identifier: NCT01574131     History of Changes
Other Study ID Numbers: 11-106
Study First Received: March 22, 2012
Last Updated: June 11, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by The University of Texas Medical Branch, Galveston:
PPAR alpha agonist
insulin sensitivity

Additional relevant MeSH terms:
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses processed this record on October 09, 2015