Type 2 DiabetesMAGNETICNCT05542147
Genetic-Dependent Cardiovascular Response to PPAR-Alpha Agonist Fenofibrate
A study testing Fenofibrate 145 mg in people with Type 2 Diabetes and Cardiovascular Diseases, run by Mario Luca Morieri at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 2 Diabetes, Cardiovascular Diseases, Pharmacogenomic Drug Interaction
- What is being tested?
- Fenofibrate 145 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- 3 Jul 2022to 30 Nov 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 9Show fewer
- Allergy to fenofibrate or excipients
- Acute / chronic pancreatitis
- Pregnancy and lactation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Physiopathological Study of Genetic Modulation of Cardiovascular Effect of PPAR-Alpha Activation (MAGNETIC-PPARA)
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.
Read the detailed description
The main hypothesis of this study is that underlying genetic heterogeneity in the CV response to fibrates can successfully identify subjects with a consistent benefit from this treatment. Supporting this postulate a common genetic variant (rs6008845) in the gene coding for PPAR-alpha has been found to dramatically influence the ability of this drug to reduce CVD events.
This genetic modulation of fenofibrate effectiveness has been found in whites, validated in black participants in the ACCORD Lipid trial, and then replicated in external cohorts. Interestingly, the genetic effect was independent of fenofibrate-induced changes in plasma lipids, suggesting a more complex mechanism of action of fibrates. (PMID:31974142).
Through this randomized study, subjects carrying the different rs6008845 genotypes (TT, TC, CC) will be randomized to receive fenofibrate or placebo for 12 weeks.
The specific aims are:
- To replicate the previous "rs6008845 by fenofibrate" interaction on MACE, testing the fenofibrate-induced changes in endothelial function, arterial stiffness, and markers of endothelium damage.
- To evaluate whether the fenofibrate-induced change on circulating biomarkers is modulated by rs6008845 genotypes. This will provide insight into the mechanism(s) behind the rs6008845 modulation of fenofibrate effectiveness by the identification of circulating biomarkers mirroring this genetic effect. Different known actions of fenofibrate, beyond lipid-lowering effects, such as fenofibrate anti-inflammatory and anti-platelet effects will be evaluated.
- Being tested
- Fenofibrate 145 mg, Placebo
- Keywords
- Diabetes, Precision Medicine, Inflammatory Response, arterial stifness, Endothelial Dysfunction, Lipid profile, Pharmacogenomic Drug Interaction, statins
- Medical subject headings
- Diabetes Mellitus, Type 2, Cardiovascular Diseases, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fenofibrate 145 mgDrug
Also called Fenofibrate
1 tablet per day
PlaceboDrug
1 tablet per day
| Study group | Role | What they receive |
|---|---|---|
| Fenofibrate | Experimental | 1 tablet per day per 12 weeks Receives: Drug: Fenofibrate 145 mg |
| Placebo | Placebo comparator | 1 tablet per day per 12 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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].
Measured: baseline and 12 weeks
Secondary outcomes (5)
Arterial Stiffness - Pulse Wave Velocity (PWV)
Differences in fenofibrate induced-changes in PWV across rs6008845 genotypes. [PWV is directly associated with risk of cardiovascular disease]
Measured: baseline and 12 weeks
Endothelial progenitor cells (EPCs)
Differences in fenofibrate induced-changes in circulating levels of EPC across rs6008845 genotypes.
Measured: baseline and 12 weeks
Inflammatory markers and chemokines
Differences in fenofibrate induced-changes in CCL11, CCL27 sVCAM, sE-Selectin, Endothelin-1 across rs6008845 genotypes.
Measured: baseline and 12 weeks
Platelet aggregation induced by adenosine diphosphate (ADP)
Anti-platelet effects will be evaluated as the differences in fenofibrate induced-changes in platelet aggregation induced by adenosine diphosphate (ADP) (i.e. ADPtest) across rs6008845 genotypes.
Measured: baseline and 12 weeks
Platelet aggregation induced by arachidonic acid
Anti-platelet effects will be evaluated as the differences in fenofibrate induced-changes in platelet aggregation induced by arachidonic acid (ASPI test) across rs6008845 genotypes.
Measured: baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2022
- Study start3 Jul 2022
- Primary completion30 Nov 2024
- Study completion30 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mario Luca Morieri
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mario Luca Morieri, University Hospital Padova
- Investigators
- Mario Luca Morieri, MD PhD, Principal investigator, University Hospital of Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05542147
- Sponsor's protocol ID
- AOP2225
- Acronym
- MAGNETIC
- Status last verified
- Aug 2025
- First submitted
- 8 Sep 2022
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 31974142Morieri 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.
PubMed 30262460Morieri 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.
PubMed 28112899
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiopathological Study of Genetic Modulation of Cardiovascular Effect of PPAR-Alpha Activation (MAGNETIC-PPARA)
- ClinicalTrials.gov ID
- NCT05542147
- Acronym / sponsor ID
- MAGNETIC / AOP2225
- Keywords
- Diabetes, Precision Medicine, Inflammatory Response, arterial stifness, Endothelial Dysfunction, Lipid profile, Pharmacogenomic Drug Interaction, statins
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Mario Luca MorieriUniversity, hospital or other
- Study start
- 3 Jul 2022 (actual)
- Primary completion
- 30 Nov 2024 (actual)
- Study completion
- 30 Nov 2024 (actual)
- First posted
- 15 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The main hypothesis of this study is that underlying genetic heterogeneity in the CV response to fibrates can successfully identify subjects with a consistent benefit from this treatment. Supporting this postulate a common genetic variant (rs6008845) in the gene coding for PPAR-alpha has been found to dramatically influence the ability of this drug to reduce CVD events.
This genetic modulation of fenofibrate effectiveness has been found in whites, validated in black participants in the ACCORD Lipid trial, and then replicated in external cohorts. Interestingly, the genetic effect was independent of fenofibrate-induced changes in plasma lipids, suggesting a more complex mechanism of action of fibrates. (PMID:31974142).
Through this randomized study, subjects carrying the different rs6008845 genotypes (TT, TC, CC) will be randomized to receive fenofibrate or placebo for 12 weeks.
The specific aims are:
- To replicate the previous "rs6008845 by fenofibrate" interaction on MACE, testing the fenofibrate-induced changes in endothelial function, arterial stiffness, and markers of endothelium damage.
- To evaluate whether the fenofibrate-induced change on circulating biomarkers is modulated by rs6008845 genotypes. This will provide insight into the mechanism(s) behind the rs6008845 modulation of fenofibrate effectiveness by the identification of circulating biomarkers mirroring this genetic effect. Different known actions of fenofibrate, beyond lipid-lowering effects, such as fenofibrate anti-inflammatory and anti-platelet effects will be evaluated.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fenofibrate | Experimental | Drug: Fenofibrate 145 mg1 tablet per day per 12 weeks |
| Placebo | Placebo comparator | Drug: Placebo1 tablet per day per 12 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fenofibrate 145 mgAlso: Fenofibrate1 tablet per day | Drug | Fenofibrate |
| Placebo1 tablet per day | Drug | Placebo |
Primary outcome
Endothelial Function
Time frame: baseline and 12 weeks
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].
5 secondary outcomes
Arterial Stiffness - Pulse Wave Velocity (PWV)
Time frame: baseline and 12 weeks
Endothelial progenitor cells (EPCs)
Time frame: baseline and 12 weeks
Inflammatory markers and chemokines
Time frame: baseline and 12 weeks
Platelet aggregation induced by adenosine diphosphate (ADP)
Time frame: baseline and 12 weeks
Platelet aggregation induced by arachidonic acid
Time frame: baseline and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2025.
- Background: PubMed 31974142Morieri 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.
- Background: PubMed 30262460Morieri 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.
- Background: PubMed 28112899Morieri 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Luca Morieri, MD PhD principal investigator
University Hospital of Padova
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fenofibrate 145 mg in people with Type 2 Diabetes and Cardiovascular Diseases, run by Mario Luca Morieri at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelial Function (time frame: baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05542147, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2025.