Genetic-Dependent Cardiovascular Response to PPAR-Alpha Agonist Fenofibrate

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Luca Morieri
• Treatments: Fenofibrate

Criteria

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