Effects of Fenofibrate on Endothelial Progenitor Cells in Diabetes

Study Overview
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Brief Summary
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Long-standing diabetes is often complicated by retinopathy. The mechanisms that induce the development of diabetic retinopathy are incompletely understood and include alterations in bone marrow derived vasculogenic cells called endothelial progenitor cells. Fenofibrate is a PPAR-alpha agonist used for the treatment of mixed dislipidemia and hypertriglyceridemia. In a trial conducted in type 2 diabetic patients, the drug fenofibrate has reduced retinopathy-related endpoints suggesting a direct effect of the drug on the mechanisms that drive the development of this complication. Herein, the investigators hypothesize that fenofibrate treatment can increase circulating EPC levels in diabetic patients with retinopathy, compared to placebo.

Detailed Description
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Long-standing diabetes is often complicated by retinopathy. The mechanisms that induce the development of diabetic retinopathy are incompletely understood and include alterations in bone marrow derived vasculogenic cells called endothelial progenitor cells. Fenofibrate is a PPAR-alpha agonist used for the treatment of mixed dislipidemia and hypertriglyceridemia. In addition to lowering triglyceride-rich lipoproteins, PPAR-alpha agonism with fenofibrate has several additional molecular benefit on the vessel wall, such as reduction of inflammation. In a trial conducted in type 2 diabetic patients, the drug fenofibrate has reduced retinopathy-related endpoints suggesting a direct effect of the drug on the mechanisms that drive the development of this complication. Preliminary data of ours on the effects of fenofibrate on cultured EPC show that this drug has the potential to improve EPC and, consequently, may benefit patients with retinopathy. Herein, the investigators hypothesize that fenofibrate treatment can increase circulating EPC levels in diabetic patients with retinopathy, compared to placebo.

Official Title
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Effects of Fenofibrate on Endothelial Progenitor Cell Levels in Diabetic Patients With Retinopathy. A Randomized Controlled Trial.

Conditions
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Diabetes, Diabetic Retinopathy

Intervention / Treatment
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* Drug: Fenofibrate 145 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 or type 2 diabetes Diabetic retinopathy Age 18-70 Both sexes Exclusion Criteria: Age <18 or >70 at enrollment Hereditary muscle disorders Uncontrolled hypothyroidism Elevated alcohol consumption Renal failure Hepatic failure Allergy to fenofibrate or excipients Acute / chronic pancreatitis Pregnancy and lactation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenofibrate<br>Fenofibrate 145 mg (Fulcrosupra) oral tablets daily for 12 weeks | Drug: Fenofibrate 145 mg<br>* Tablets of Fulcrosupra 145 mg to be taken at 8.00 am daily for 12 weeks.<br>* Other names: Fulcrosupra 145 mg;|
| Placebo Comparator: Placebo<br>Placebo oral tablets daily for 12 weeks | Drug: Placebo<br>* Oral Placebo tablets once daily<br>* Other names: Placebo control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial progenitor cells | Change in endothelial progenitor cell (EPC) levels in fenofibrate-treated vs placebo-treated patients over 12 weeks. | 12 weeks | 
| Circulating progenitor cells | Change in circulating progenitor cell (CPC) levels in fenofibrate-treated vs placebo-treated patients over 12 weeks. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Triglycerides | Change in Triglycerideslevels in fenofibrate-treated vs placebo-treated patients over 12 weeks. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cells, Regeneration, Angiogenesis, Prevention