Effects of Fenofibrate on Endothelial Progenitor Cells in Diabetes

Conditions

Diabetes, Diabetic Retinopathy

Keywords

Stem cells, Regeneration, Angiogenesis, Prevention

Brief summary

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

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.

Bonora BM, Albiero M, Morieri ML, Cappellari R, Amendolagine FI, Mazzucato M, Zambon A, Iori E, Avogaro A, Fadini GP.

2021-08-0915 citations

10.1007/s00125-021-05532-1

Papers published before 2007-09-01 may not appear yet. Historical indexing is in progress.

Interventions

DRUGFenofibrate 145 mg

Tablets of Fulcrosupra 145 mg to be taken at 8.00 am daily for 12 weeks.

DRUGPlacebo

Oral Placebo tablets once daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

SINGLE (Subject)

Masking description

Single blind

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

No

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.

Design outcomes

Primary

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

Secondary

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

Countries

Italy

Outcome results

None listed