BurnPhase 2/3NCT00732485
Mitochondrial Oxidation and Insulin Resistance in Burn Patients Treated With Fenofibrate
A Phase 2/3 study testing fenofibrate in people with Burn, run by The University of Texas Medical Branch, Galveston.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 20 years
- Conditions the study is for
- Burn
- What is being tested?
- fenofibrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Aug 2008to Dec 2013
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients > 7 years old with burns covering 40% or more of body surface who are admitted to the Shriners Hospital for Children, Galveston, Texas
Who cannot join
- Abnormal liver and kidney function,
- Pregnancy,
- Diabetes mellitus,
About this study
Official title: The Role of Mitochondrial Oxidation on Insulin Resistance in Burn Patients Treated With Fenofibrate
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:
- Will fenofibrate given to burn patients with insulin resistance restore their insulin sensitivity?
- What is the relationship between mitochondrial dysfunction in muscle tissue as the causative mechanism of burn related insulin resistance?
- 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?
Read the detailed description
The following specific hypotheses will be investigated:
- 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.
- 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.
- 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.
- 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.
- Treatment of patients with the peroxisome proliferator-activated receptor (PPAR) alpha agonist 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.
- Conditions
- Burn
- Being tested
- fenofibrate, placebo
- Keywords
- Burn injury, Fenofibrate, Insulin resistance, Mitochondrial function, Fat oxidation, PPAR, Protein, Glucose, Wound
- Medical subject headings
- Burns, Insulin Resistance, Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fenofibrateDrug
Fenofibrate, PO, 5 mg/kg/day from admission to 6 months post burn
placeboDrug
Placebo, sugar pill, from admission to 6 months post burn
| Study group | Role | What they receive |
|---|---|---|
| Fenofibrate | Active comparator | Not described Receives: Drug: fenofibrate |
| Placebo | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity on glucose and protein metabolism
Measured: From admission to burn unit to 6 months post burn
Secondary outcomes (3)
Systemic glucose homeostasis
Measured: Admission to 6 months post burn
Muscle protein balance
Measured: Admission to 6 months post burn
Wound protein balance
Measured: Admission to 6 months post burn
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionDec 2012 (estimated)
- Study completionDec 2013 (estimated)
Why it stopped: Principal Investigator Changed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BurnStudies of the same condition, open and under way.
- More trials run by The University of Texas Medical Branch, GalvestonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Shriners Hospitals for Children
- Responsible party
- Sponsor
- Investigators
- David Herndon, MD, Principal investigator, University of Texas Medical Branch, Galveston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00732485
- Sponsor's protocol ID
- 07-389
- Other IDs
- SHC 08-GAL-006
- Status last verified
- Dec 2012
- First submitted
- 8 Aug 2008
- Last updated
- 11 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cree MG, Zwetsloot JJ, Herndon DN, Qian T, Morio B, Fram R, Sanford AP, Aarsland A, Wolfe RR. Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Ann Surg. 2007 Feb;245(2):214-21. doi: 10.1097/01.sla.0000250409.51289.ca.
PubMed 17245174
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Mitochondrial Oxidation on Insulin Resistance in Burn Patients Treated With Fenofibrate
- ClinicalTrials.gov ID
- NCT00732485
- Acronym / sponsor ID
- 07-389
- Conditions
- Burn
- Keywords
- Burn injury, Fenofibrate, Insulin resistance, Mitochondrial function, Fat oxidation, PPAR, Protein, Glucose
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Principal Investigator Changed
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The University of Texas Medical Branch, GalvestonUniversity, hospital or other
- Collaborators
- Shriners Hospitals for Children
- Study start
- Aug 2008
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 12 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Will fenofibrate given to burn patients with insulin resistance restore their insulin sensitivity?
- What is the relationship between mitochondrial dysfunction in muscle tissue as the causative mechanism of burn related insulin resistance?
- 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?
Detailed description
The following specific hypotheses will be investigated:
- 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.
- 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.
- 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.
- 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.
- Treatment of patients with the peroxisome proliferator-activated receptor (PPAR) alpha agonist 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fenofibrate | Active comparator | Drug: fenofibrate |
| Placebo | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 7 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Patients > 7 years old with burns covering 40% or more of body surface who are admitted to the Shriners Hospital for Children, Galveston, Texas
Key exclusion criteria (3 listed)
- Abnormal liver and kidney function,
- Pregnancy,
- Diabetes mellitus,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fenofibrateFenofibrate, PO, 5 mg/kg/day from admission to 6 months post burn | Drug | Fenofibrate |
| placeboPlacebo, sugar pill, from admission to 6 months post burn | Drug | Placebo |
Primary outcome
Insulin sensitivity on glucose and protein metabolism
Time frame: From admission to burn unit to 6 months post burn
3 secondary outcomes
Systemic glucose homeostasis
Time frame: Admission to 6 months post burn
Muscle protein balance
Time frame: Admission to 6 months post burn
Wound protein balance
Time frame: Admission to 6 months post burn
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2012.
- Results publication: PubMed 17245174Cree MG, Zwetsloot JJ, Herndon DN, Qian T, Morio B, Fram R, Sanford AP, Aarsland A, Wolfe RR. Insulin sensitivity and mitochondrial function are improved in children with burn injury during a randomized controlled trial of fenofibrate. Ann Surg. 2007 Feb;245(2):214-21. doi: 10.1097/01.sla.0000250409.51289.ca.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Herndon, MD principal investigator
University of Texas Medical Branch, Galveston
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing fenofibrate in people with Burn, run by The University of Texas Medical Branch, Galveston.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin sensitivity on glucose and protein metabolism (time frame: From admission to burn unit to 6 months post burn). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00732485, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2012.