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

This study is currently recruiting participants.
Verified December 2013 by The University of Texas, Galveston
Sponsor:
Collaborator:
Shriners Hospitals for Children
Information provided by (Responsible Party):
The University of Texas, Galveston
ClinicalTrials.gov Identifier:
NCT01574131
First received: March 22, 2012
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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, 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 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar pill
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.

  Eligibility

Ages Eligible for Study:   4 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01574131

Contacts
Contact: Mike Kinsky, MD mkinsky@utmb.edu
Contact: Cathy L Reed, BSN 409-770-6987 ca2reed@utmb.edu

Locations
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77551
Contact: Mike Kinsky, MD       mkinsky@utmb.edu   
Contact: Cathy L Reed, BSN    409-770-6987    ca2reed@utmb.edu   
Principal Investigator: Mike Kinsky, MD         
Sponsors and Collaborators
The University of Texas, Galveston
Shriners Hospitals for Children
Investigators
Principal Investigator: Mike Kinsky, MD University of Texas
  More Information

No publications provided

Responsible Party: The University of Texas, Galveston
ClinicalTrials.gov Identifier: NCT01574131     History of Changes
Other Study ID Numbers: 11-106
Study First Received: March 22, 2012
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by The University of Texas, Galveston:
Burn
Fenofibrate
PPAR alpha agonist
insulin sensitivity
mitochondrial

Additional relevant MeSH terms:
Fenofibrate
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014