CompletedNot Applicable

Genetic-Dependent Cardiovascular Response to PPAR-Alpha Agonist Fenofibrate

Italy200 participantsStarted 2022-07-03

Plain-language summary

Fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-a) agonist known to improve diabetic dyslipidemia, has been proposed as a drug to prevent cardiovascular disease (CVD) in type 2 diabetes (T2D). However, the results of clinical trials have been mixed. Supporting the hypothesis that these disappointing results hide a genetic heterogeneity in the CVD response to fenofibrate, a common genetic variant (rs6008845) in the gene coding for PPAR-a has been found to dramatically influence the ability of this drug to reduce CVD events in the ACCORD Lipid trial (PMID:31974142). The aim of this study is to validate these findings by dissecting the pathways and mechanism through which this variant exerts such a modulatory effect, by means of a randomized clinical trial. If successful, this project will pave the way to a precision medicine approach to prescribe fenofibrate optimally, offering a cardio-protective drug to those patients that are most likely to experience a robust benefit from this medication.

Who can participate

Age range18 Years – 75 Years

SexALL

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Inclusion Criteria: * Type 2 diabetes with previous cardiovascular events or at least one CV risk factor (hypertension, obesity, smoke, age\>65 years) * HbA1c \< 8% * Triglycerides \< 200 mg/dl * On statin treatments and with LDLcholesterol \< 100 mg/dl or at maximum statin-tolerated dose * European ancestry (rational: given the relatively small sample size and the ancestry-differences in allele frequency of rs6008845 T allele \[i.e. from 65% in whites to 20% in blacks subjects) this criteria allows to limit ethnic-confounding factors that would reduce the probability of success of this physiopathological study aiming to dissect the mechanism of the genetic modulation of fenofibrate effectiveness). Exclusion Criteria: * CKD III stage with eGFR\<60 ml/min/1.73 * Uncontrolled hypertension with systolic blood pressure \> 170 mmHg at enrollment. * Hereditary muscle disorders * Uncontrolled hypothyroidism * Elevated alcohol consumption * Hepatic failure * Allergy to fenofibrate or excipients * Acute / chronic pancreatitis * Pregnancy and lactation

What they're measuring

Endothelial Function

Timeframe: baseline and 12 weeks

Trial details

NCT IDNCT05542147

SponsorMario Luca Morieri

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-11-30