Myocardial Reperfusion InjuryPhase 4PREVALENTNCT05775380
The Role of Pioglitazone in Vascular Transcriptional Remodeling
A Phase 4 study testing Pioglitazone 45 mg in people with Myocardial Reperfusion Injury, run by University of Campinas, Brazil at 1 site in Brazil.
Trial summary
Acute myocardial infarction (AMI) remains the leading cause of death worldwide. In this scenario, early coronary reperfusion is the main therapeutic strategy as it substantially reduces mortality. Read more about this study
- Who is it for?
- Ages 40 to 70 years, men only
- Conditions the study is for
- Myocardial Reperfusion Injury
- What is being tested?
- Pioglitazone 45 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteBrazil
- Study dates
- 15 Jun 2023to 22 Dec 2024
- Phase
- Phase 4
- 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 40 to 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male individuals
- Individuals undergoing CABG surgery for coronary artery disease
- Be over 40 years of age
- BMI between 20 and 34.9kg/m2
- Non-diabetic or if diabetic, disease duration < 10 years, Hba1c < 8%, non-user of NPH insulin
- Ejection fraction > 40%
- Glomerular filtration rate > 45 mL/min
Who cannot join
- BMI greater than 35 kg/m2, steatohepatitis, chronic kidney disease, systemic vasculitis, conditions that induce systemic inflammation such as psoriasis and systemic lupus erythematosus
- contraindications to the use of pioglitazone hydrochloride (heart failure, liver failure - AST or ALT > 2.5x upper normal limit, history of bladder cancer or macroscopic hematuria without investigation)
- moderate or severe valve disease
- need for concomitant use of other hypoglycemic therapies during hospitalization, particularly insulin
- peripheral edema
- recent hospitalization
Show all 12Show fewer
- known allergy to any study drug
- polyuria, polydipsia, weight loss, or other clinical signs of volume depletion or diabetes, difficult-to-control systemic arterial hypertension, defined as individuals taking 4 or more drugs
- those who withdraw the Informed Consent Form (TCLE), or who, for some reason, are not able to sign or understand the TCLE
- history of gastrointestinal disorders that may interfere with study drug absorption
- research participant who is participating in other clinical trials or whose participation ended less than six months ago
- Research participant who has left ventricular dysfunction
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
University of Campinas
Campinas, São Paulo, 13083-887
Andrei C Sposito, MD, PhD, +551935218788, sposito@unicamp.br
Andrei C Sposito, MD, PhD
About this study
Official title: The Role of Pioglitazone in Vascular Transcriptional Remodeling in Individuals Undergoing Coronary Artery Bypass Grafting
Acute myocardial infarction (AMI) remains the leading cause of death worldwide. In this scenario, early coronary reperfusion is the main therapeutic strategy as it substantially reduces mortality. Paradoxically, however, reperfusion triggers additional tissue damage that accounts for about 50% of the infarcted heart mass, i.e., ischemia and reperfusion injury (IRL). In this context, sphingosine-1-phosphate (S1P) is a sphingolipid synthesized by sphingosine kinases (Sphk), carried in plasma bound to high-density lipoprotein (HDL) and released after cellular damage such as LIR. Particularly, in animal models of AMI, therapies targeting downstream S1P receptor signaling triggered by HDL/S1P are able to promote endothelial barrier functions and attenuate secondary damage to LIR. Thus, the molecular control of sphingosine kinase 1 (Sphk1) transcription during LIR in vivo or during hypoxia/reoxygenation (H/R) in vitro may represent an important mechanism for maintaining endothelial homeostasis since it promotes the generation of S1P and this may promote subsequent HDL enrichment. Thus, the role of pioglitazone hydrochloride 45mg/day for five days in volunteers undergoing coronary artery bypass grafting (BVR) will be investigated in order to verify the vascular expression of SPhk1, transcriptome and vascular proteome remodeling, as well as S1P content in HDL.
Read the detailed description
This will be a prospective, randomized and open clinical study. From a sample of patients hospitalized for myocardial revascularization surgery, followed at the cardiac surgery outpatient clinic, 20 research participants, male, aged over 40 years, non-diabetic or diabetic with disease duration of less than 10 years, glycated hemoglobin <8% and non-user of NPH insulin, body mass index (BMI) between 20 and 34.9kg/m2 and glomerular filtration rate above 45mL/min who will be monitored at the Hospital de Clínicas/UNICAMP and randomized to receive pioglitazone hydrochloride 45mg/day for 5 days before surgery. The amount of S1P in HDL at baseline (before surgery) will be assessed. This same measurement will be repeated on day 5 (coinciding with the day of surgery) after using pioglitazone hydrochloride 45mg/day. In addition, on the day of surgery, a saphenous vein fragment of approximately 2 cm and an internal thoracic artery fragment of approximately 1 cm will be collected, which will not impair the quality of the graft nor the extent of the material to be used as a graft, because in this case the vascular material is abundant. An aortic artery button and an atrial appendage button will also be collected, which will be discarded. In addition, the results of serum troponin levels in the first 24h post-SVR (6, 12, 24h) will be evaluated to estimate the extent of troponin release. Postoperative examination.
- Conditions
- Myocardial Reperfusion Injury
- Being tested
- Pioglitazone 45 mg
- Medical subject headings
- Myocardial Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone 45 mgDrug
Also called pioglitazone hydrochloride
We investigated the role of pioglitazone hydrochloride 45mg/day for five days in patients admitted for coronary artery bypass grafting (CABG) in order to investigate vascular SPhk1 expression, vascular transcriptome and proteome remodeling, as well as S1P content in HDL
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Active comparator | Research participants will be randomized to receive pioglitazone hydrochloride 45mg/day for 5 days prior to coronary artery bypass surgery. Receives: Drug: Pioglitazone 45 mg |
| Placebo | No intervention | Research participants will be randomized to not receive intervention in the days prior to coronary artery bypass graft surgery. |
What is being measured
The primary outcome is the main question the study is designed to answer.
HDL-S1P change
Change in S1P content of isolated HDL between baseline and after treatment with pioglitazone hydrochloride 45 mg/day
Measured: Five days
Secondary outcomes (4)
SPHK1 - internal thoracic artery
Difference in SPHK1 expression in the internal thoracic artery cells determined by western blot between groups
Measured: Five days
S1PR1 - saphenous vein
Difference in S1P receptor (S1PR1) expression in saphenous vein endothelial cells determined by western blot between groups
Measured: Five days
SPHK1 - aortic artery
Difference in SPHK1 expression in the aortic artery cells determined by western blot between groups;
Measured: Five days
SPHK1 - atrial appendage
Difference in SPHK1 expression in the atrial appendage cells determined by western blot between groups;
Measured: Five days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start15 Jun 2023
- Primary completion28 Jun 2024 (estimated)
- Study completion22 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myocardial Reperfusion InjuryStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Campinas, Brazil
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrei Carvalho Sposito, University of Campinas, Brazil
- Investigators
- Andrei Sposito, Professor, Principal investigator, University of Campinas, Brazil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05775380
- Sponsor's protocol ID
- PREVALENT
- Acronym
- PREVALENT
- Status last verified
- Jan 2024
- First submitted
- 7 Mar 2023
- Last updated
- 12 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Pioglitazone in Vascular Transcriptional Remodeling in Individuals Undergoing Coronary Artery Bypass Grafting
- ClinicalTrials.gov ID
- NCT05775380
- Acronym / sponsor ID
- PREVALENT / PREVALENT
- Conditions
- Myocardial Reperfusion Injury
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of Campinas, BrazilUniversity, hospital or other
- Study start
- 15 Jun 2023 (actual)
- Primary completion
- 28 Jun 2024 (estimated)
- Study completion
- 22 Dec 2024 (estimated)
- First posted
- 20 Mar 2023 (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.
Acute myocardial infarction (AMI) remains the leading cause of death worldwide. In this scenario, early coronary reperfusion is the main therapeutic strategy as it substantially reduces mortality. Paradoxically, however, reperfusion triggers additional tissue damage that accounts for about 50% of the infarcted heart mass, i.e., ischemia and reperfusion injury (IRL). In this context, sphingosine-1-phosphate (S1P) is a sphingolipid synthesized by sphingosine kinases (Sphk), carried in plasma bound to high-density lipoprotein (HDL) and released after cellular damage such as LIR. Particularly, in animal models of AMI, therapies targeting downstream S1P receptor signaling triggered by HDL/S1P are able to promote endothelial barrier functions and attenuate secondary damage to LIR. Thus, the molecular control of sphingosine kinase 1 (Sphk1) transcription during LIR in vivo or during hypoxia/reoxygenation (H/R) in vitro may represent an important mechanism for maintaining endothelial homeostasis since it promotes the generation of S1P and this may promote subsequent HDL enrichment. Thus, the role of pioglitazone hydrochloride 45mg/day for five days in volunteers undergoing coronary artery bypass grafting (BVR) will be investigated in order to verify the vascular expression of SPhk1, transcriptome and vascular proteome remodeling, as well as S1P content in HDL.
Detailed description
This will be a prospective, randomized and open clinical study. From a sample of patients hospitalized for myocardial revascularization surgery, followed at the cardiac surgery outpatient clinic, 20 research participants, male, aged over 40 years, non-diabetic or diabetic with disease duration of less than 10 years, glycated hemoglobin <8% and non-user of NPH insulin, body mass index (BMI) between 20 and 34.9kg/m2 and glomerular filtration rate above 45mL/min who will be monitored at the Hospital de Clínicas/UNICAMP and randomized to receive pioglitazone hydrochloride 45mg/day for 5 days before surgery. The amount of S1P in HDL at baseline (before surgery) will be assessed. This same measurement will be repeated on day 5 (coinciding with the day of surgery) after using pioglitazone hydrochloride 45mg/day. In addition, on the day of surgery, a saphenous vein fragment of approximately 2 cm and an internal thoracic artery fragment of approximately 1 cm will be collected, which will not impair the quality of the graft nor the extent of the material to be used as a graft, because in this case the vascular material is abundant. An aortic artery button and an atrial appendage button will also be collected, which will be discarded. In addition, the results of serum troponin levels in the first 24h post-SVR (6, 12, 24h) will be evaluated to estimate the extent of troponin release. Postoperative examination.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Active comparator | Drug: Pioglitazone 45 mgResearch participants will be randomized to receive pioglitazone hydrochloride 45mg/day for 5 days prior to coronary artery bypass surgery. |
| Placebo | No intervention | –Research participants will be randomized to not receive intervention in the days prior to coronary artery bypass graft surgery. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male individuals
- Individuals undergoing CABG surgery for coronary artery disease
- Be over 40 years of age
- BMI between 20 and 34.9kg/m2
- Non-diabetic or if diabetic, disease duration < 10 years, Hba1c < 8%, non-user of NPH insulin
Key exclusion criteria (12 listed)
- BMI greater than 35 kg/m2, steatohepatitis, chronic kidney disease, systemic vasculitis, conditions that induce systemic inflammation such as psoriasis and systemic lupus erythematosus
- contraindications to the use of pioglitazone hydrochloride (heart failure, liver failure - AST or ALT > 2.5x upper normal limit, history of bladder cancer or macroscopic hematuria without investigation)
- moderate or severe valve disease
- need for concomitant use of other hypoglycemic therapies during hospitalization, particularly insulin
- peripheral edema
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 |
|---|---|---|
| Pioglitazone 45 mgAlso: pioglitazone hydrochlorideWe investigated the role of pioglitazone hydrochloride 45mg/day for five days in patients admitted for coronary artery bypass grafting (CABG) in order to investigate vascular SPhk1 expression, vascular transcriptome and proteome remodeling, as well as S1P content in HDL | Drug | Pioglitazone |
Primary outcome
HDL-S1P change
Time frame: Five days
Change in S1P content of isolated HDL between baseline and after treatment with pioglitazone hydrochloride 45 mg/day
4 secondary outcomes
SPHK1 - internal thoracic artery
Time frame: Five days
S1PR1 - saphenous vein
Time frame: Five days
SPHK1 - aortic artery
Time frame: Five days
SPHK1 - atrial appendage
Time frame: Five days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2024.
- Individual participant dataSharing planned: No
Related trials for Myocardial Reperfusion Injury
RecruitingPhase 2
Prevention of Reperfusion Injury Outcomes Through Effective Cardioprotection Targeting Myocardial Infarction
Myocardial Infarction, Reperfusion Injury
Not yet recruitingPhase 2
Evaluating SGLT2 Inhibitors for the Reduction of No-Reflow Phenomenon in Patients Undergoing PCI
No Reflow Phenomenon, Reperfusion Injuries, Myocardial
RecruitingObservational study
Spectroscopic Assessment of Myocardial Oxygenation Changes in Pediatric Heart Surgery
Myocardial Ischemia, Heart Defects, Congenital
Active, not recruitingPhase 2
Effect of L-Carnitine on Biomarkers of Myocardial Reperfusion Injury in Patients With STEMI
Reperfusion Injury, Myocardial, Myocardial Infarction
Not yet recruitingPhase 2
Combined Antioxidant Therapy for Acute Myocardial Infarction
Acute Myocardial Infarction (AMI), ST Elevation (STEMI) Myocardial Infarction
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.
Andrei Sposito, Professor principal investigator
University of Campinas, Brazil
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pioglitazone 45 mg in people with Myocardial Reperfusion Injury, run by University of Campinas, Brazil at 1 site in Brazil.
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 7 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 12 Jan 2024. 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 Brazil. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrei Sposito, Professor (+551935218788, sposito@unicamp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HDL-S1P change (time frame: Five days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jan 2024; AzTrials last refreshed its copy on 8 Nov 2026.