Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000671066
Ethics application status
Not yet submitted
Date submitted
16/08/2010
Date registered
16/08/2010
Date last updated
16/08/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
Fenofibrate effects on endothelial progenitor cell (EPC) number and function
Scientific title
Fenofibrate effects on endothelial progenitor cell (EPC) number and function in patients with recent diagnosis of type 2 diabetes mellitus (T2DM).
Secondary ID [1] 252452 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes mellitus 257963 0
Hypercholesterolemia/dyslipidemia 257964 0
Condition category
Condition code
Cardiovascular 258131 258131 0 0
Diseases of the vasculature and circulation including the lymphatic system
Metabolic and Endocrine 258132 258132 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Commencement of fenofibrate 145mg tablets orally as a single dose daily for 6 weeks. At the end of the 6 week period, half the subjects selected randomly will receive additional atorvastatin 40mg daily taken orally and the other half will continue with fenofibrate 145mg only for a further 6 weeks . At the end of the 12 week treatment period, all intervention treatment will be ceased and subjects analysed 6 weeks later.
Intervention code [1] 257018 0
Treatment: Drugs
Comparator / control treatment
Patients on treatment will act as controls with assesment of EPC number/function at baseline, and subsequent comparison of patients on fenofibrate only versus combination of fenofibrate plus atorvatstain.
Control group
Active

Outcomes
Primary outcome [1] 258995 0
Change in EPC number using flow cytometric analysis.
Timepoint [1] 258995 0
Assessments done at baseline, 6, 12 and at 18 weeks.
Primary outcome [2] 258996 0
EPC function using standardized colony forming unit assays and by in vitro angiogenesis assays using Matrigel. Serum angiogenic factors will be quantified by Enzyme Linked Immunosorbent Assay (ELISA).
Timepoint [2] 258996 0
Assessments done at baseline, 6, 12 and at 18 weeks.
Secondary outcome [1] 265206 0
Nil
Timepoint [1] 265206 0
N/A

Eligibility
Key inclusion criteria
1)Recently diagnosed type 2 diabetes mellitus in adults.
2) No previous recent exposure to or any current definite indication for statins or fibrates
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Age less than 18 years
2) Pregnant women(based on urine Beta Human Choriogonadotrophin test (HCG))
3) Cognitively impaired, homeless people or others considered unlikely to comply.
4) Acute myocardial infarction within the last 3 months
5) Anemia with Hemoglobin < 110 mg/dl
6) Significant renal impairment (estimated Glomerular Filtration Rate<60 ml/min/1.73m^2)
7) Active liver disease
8) Clinical gallbladder disease
9)Known hypersensitivity to statin or fibrate therapy
10) Severe hypertriglyceridaemia and/or pancreatitis requiring fibrate therapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
22
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 257471 0
University
Name [1] 257471 0
National Health and Medical Research Council, Clinical Trials Centre, University of Sydney
Country [1] 257471 0
Australia
Primary sponsor type
Individual
Name
Prof Anthony Keech
Address
Locked Bag 77, Camperdown NSW 1450
Country
Australia
Secondary sponsor category [1] 256698 0
None
Name [1] 256698 0
Address [1] 256698 0
Country [1] 256698 0
Other collaborator category [1] 251441 0
Individual
Name [1] 251441 0
Dr Martin Ng
Address [1] 251441 0
Heart Research Institute, 7 Eliza Street Newtown, NSW 2042
Country [1] 251441 0
Australia
Other collaborator category [2] 251442 0
Individual
Name [2] 251442 0
Prof Roland Stocker
Address [2] 251442 0
Room 253, Medical Foundation Building, K25, 92-94 Parramatta Rd, Camperdown, NSW 2050
Country [2] 251442 0
Australia
Other collaborator category [3] 251443 0
Individual
Name [3] 251443 0
Dr Kushwin Rajamani
Address [3] 251443 0
Locked Bag 77, Camperdown NSW 1450
Country [3] 251443 0
Australia
Other collaborator category [4] 251444 0
Individual
Name [4] 251444 0
Dr Linda Hoffman
Address [4] 251444 0
Room 154, Medical Foundation Building, K25, 92-94 Parramatta Rd, Camperdown, NSW 2050
Country [4] 251444 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 259496 0
Ethics committee address [1] 259496 0
Ethics committee country [1] 259496 0
Date submitted for ethics approval [1] 259496 0
30/06/2010
Approval date [1] 259496 0
Ethics approval number [1] 259496 0
X10-0192

Summary
Brief summary
BACKGROUND AND SCIENTIFIC BASIS
Coronary artery disease is an important cause of morbidity and mortality worldwide. Although much is known about the mechanism of myocardial infarction and its associated risk factors, many patients develop myocardial infarction in the absence of known risk factors. Two possible explanations for this are impaired angiogenesis (new blood vessel formation) and impaired endothelial (blood vessel lining) reparative processes in this group of patients. Endothelial progenitor cells (EPC) are thought to be involved in these two processes by: 1) incorporating into new vessels, or 2) coordinating the reparative process.

Fenofibrate is a lipid-lowering agent, used in the setting of hypercholesterolemia, particularly among patients with coronary artery disease and diabetes. It has well documented beneficial effects by reducing myocardial infarction. In practice, it is commonly used when patients are intolerant of statins (another cholesterol lowering agent), or in combination with statins. Interest in fenofibrate has increased with recent observations of reduced diabetic microvascular complications.

Little is known about EPCs and their function. It has been recently shown that EPCs derived from bone marrow circulate in the peripheral blood and can facilitate the formation of new blood vessels in tissues that are not getting enough blood supply, thereby helping to increase the blood supply to the affected tissue (Asahara T et al Science. 1997;275:964, Urbich C. Circ Res. 2004;95:343). Moreover, patients with coronary artery disease who have high blood levels of EPCs have a better prognosis than those with low EPC levels, possibly due to the beneficial reparative effects of these cells (Werner N. N Engl J Med 2005;353:999). It is unknown if the clinical outcomes of fenofibrate are partly related to EPC levels and function. Statins have been shown to have a positive effect on EPC number and function when used alone. Their effects in combination with fenofibrate have not been evaluated.

HYPOTHESIS
The central hypotheses of this project are that: 1) EPC levels are increased by fenofibrate 2) EPC levels are higher in those with vascular disease, 3) Fenofibrate augments EPC differentiation and function and 4) Effects of fenofibrate on EPC s occur with and without combination statin therapy.

AIMS
1.To determine the number of EPC s after fenofibrate treatment.
2.To investigate if fenofibrate augments EPC function and number.
3.To see the additional benefit of statins on EPC number and function.


POTENTIAL SIGNIFICANCE
This study will be one of the preliminary studies in man, to identify if fenofibrate has a positive effect on EPCs, and provide an understanding of the clinical effects observed. This will have implications in understanding the role of EPCs in the pathogenesis of vascular diseases, as well as in the development of novel treatment strategies for reducing the impact of vascular disease and myocardial infarction.
Trial website
Nil
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31524 0
Address 31524 0
Country 31524 0
Phone 31524 0
Fax 31524 0
Email 31524 0
Contact person for public queries
Name 14771 0
Dr Kushwin Rajamani
Address 14771 0
Locked Bag 77,
Camperdown NSW 1450
Country 14771 0
Australia
Phone 14771 0
+61 413540679
Fax 14771 0
Email 14771 0
kushwin79@yahoo.co.uk
Contact person for scientific queries
Name 5699 0
Dr Kushwin Rajamani
Address 5699 0
Locked Bag 77,
Camperdown NSW 1450
Country 5699 0
Australia
Phone 5699 0
+61 413540679
Fax 5699 0
Email 5699 0
kushwin79@yahoo.co.uk

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.