NCT05542147

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for not_applicable type-2-diabetes

Timeline
Completed

Started Jul 2022

Typical duration for not_applicable type-2-diabetes

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 3, 2022

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 8, 2022

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 15, 2022

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2024

Completed
Last Updated

August 11, 2025

Status Verified

August 1, 2025

Enrollment Period

2.4 years

First QC Date

September 8, 2022

Last Update Submit

August 6, 2025

Conditions

Type 2 DiabetesCardiovascular DiseasesPharmacogenomic Drug Interaction

Keywords

DiabetesPrecision MedicineInflammatory Responsearterial stifnessEndothelial DysfunctionLipid profilePharmacogenomic Drug Interactionstatins

Outcome Measures

Primary Outcomes (1)

  • Endothelial Function

    Differences in fenofibrate induced-changes in Reactive Hyperemia Index (RHI) across rs6008845 genotypes. \[RHI is a non-invasive measure of endothelial function, and it is inversely associated with risk of cardiovascular disease\].

    baseline and 12 weeks

Secondary Outcomes (5)

  • Arterial Stiffness - Pulse Wave Velocity (PWV)

    baseline and 12 weeks

  • Endothelial progenitor cells (EPCs)

    baseline and 12 weeks

  • Inflammatory markers and chemokines

    baseline and 12 weeks

  • Platelet aggregation induced by adenosine diphosphate (ADP)

    baseline and 12 weeks

  • Platelet aggregation induced by arachidonic acid

    baseline and 12 weeks

Other Outcomes (2)

  • Arterial Stiffness - Augmentation Index (AI)

    Baseline and 12 weeks

  • Haematopoietic stem/progenitor cells (HSPCs)

    Baseline and 12 weeks

Study Arms (2)

Fenofibrate

EXPERIMENTAL

1 tablet per day per 12 weeks

Drug: Fenofibrate 145 mg

Placebo

PLACEBO COMPARATOR

1 tablet per day per 12 weeks

Drug: Placebo

Interventions

Fenofibrate 145 mgDRUG

1 tablet per day

Also known as: Fenofibrate
Fenofibrate
PlaceboDRUG

1 tablet per day

Placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital of Padova

Padua, Padua, 35128, Italy

Location

Related Publications (3)

  • Morieri ML, Shah HS, Sjaarda J, Lenzini PA, Campbell H, Motsinger-Reif AA, Gao H, Lovato L, Prudente S, Pandolfi A, Pezzolesi MG, Sigal RJ, Pare G, Marcovina SM, Rotroff DM, Patorno E, Mercuri L, Trischitta V, Chew EY, Kraft P, Buse JB, Wagner MJ, Cresci S, Gerstein HC, Ginsberg HN, Mychaleckyj JC, Doria A. PPARA Polymorphism Influences the Cardiovascular Benefit of Fenofibrate in Type 2 Diabetes: Findings From ACCORD-Lipid. Diabetes. 2020 Apr;69(4):771-783. doi: 10.2337/db19-0973. Epub 2020 Jan 23.

    PMID: 31974142BACKGROUND

  • Morieri ML, Gao H, Pigeyre M, Shah HS, Sjaarda J, Mendonca C, Hastings T, Buranasupkajorn P, Motsinger-Reif AA, Rotroff DM, Sigal RJ, Marcovina SM, Kraft P, Buse JB, Wagner MJ, Gerstein HC, Mychaleckyj JC, Pare G, Doria A. Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial. Diabetes Care. 2018 Nov;41(11):2404-2413. doi: 10.2337/dc18-0709. Epub 2018 Sep 27.

    PMID: 30262460BACKGROUND

  • Morieri ML, Shah H, Doria A; the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Genetic Study Group. Variants in ANGPTL4 and the Risk of Coronary Artery Disease. N Engl J Med. 2016 Dec 8;375(23):2304-2305. doi: 10.1056/NEJMc1607380. No abstract available.

    PMID: 28112899BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Cardiovascular DiseasesDiabetes Mellitus

Interventions

Fenofibrate

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Fibric AcidsIsobutyratesButyratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsPhenyl EthersEthersBenzophenonesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPhenolsKetones

Study Officials

  • Mario Luca Morieri, MD PhD

    University Hospital of Padova

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
Single-blinded for treatment (Participant), double-blinded for genetics (Participant and Investigator)
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

September 8, 2022

First Posted

September 15, 2022

Study Start

July 3, 2022

Primary Completion

November 30, 2024

Study Completion

November 30, 2024

Last Updated

August 11, 2025

Record last verified: 2025-08

Locations

IT(1)