Back to resultsThe Role of Pioglitazone in Vascular Transcriptional Remodeling (PREVALENT)
Primary Purpose
Myocardial Reperfusion Injury
Status
Recruiting
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Pioglitazone 45 mg
Sponsored by
About this trial
This is an interventional prevention trial for Myocardial Reperfusion Injury
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
Sites / Locations
- University of CampinasRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
No Intervention
Arm Label
Pioglitazone
Placebo
Arm Description
Research participants will be randomized to receive pioglitazone hydrochloride 45mg/day for 5 days prior to coronary artery bypass surgery.
Research participants will be randomized to not receive intervention in the days prior to coronary artery bypass graft surgery.
Outcomes
Primary Outcome Measures
HDL-S1P change
Change in S1P content of isolated HDL between baseline and after treatment with pioglitazone hydrochloride 45 mg/day
Secondary Outcome Measures
SPHK1 - internal thoracic artery
Difference in SPHK1 expression in the internal thoracic artery cells determined by western blot between groups
S1PR1 - saphenous vein
Difference in S1P receptor (S1PR1) expression in saphenous vein endothelial cells determined by western blot between groups
SPHK1 - aortic artery
Difference in SPHK1 expression in the aortic artery cells determined by western blot between groups;
SPHK1 - atrial appendage
Difference in SPHK1 expression in the atrial appendage cells determined by western blot between groups;
Full Information
NCT ID
NCT05775380
First Posted
March 7, 2023
Last Updated
July 5, 2023
Sponsor
University of Campinas, Brazil
1. Study Identification
Unique Protocol Identification Number
NCT05775380
Brief Title
The Role of Pioglitazone in Vascular Transcriptional Remodeling
Acronym
PREVALENT
Official Title
The Role of Pioglitazone in Vascular Transcriptional Remodeling in Individuals Undergoing Coronary Artery Bypass Grafting
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2023 (Actual)
Primary Completion Date
November 27, 2023 (Anticipated)
Study Completion Date
December 22, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Campinas, Brazil
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Reperfusion Injury
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pioglitazone
Arm Type
Active Comparator
Arm Description
Research participants will be randomized to receive pioglitazone hydrochloride 45mg/day for 5 days prior to coronary artery bypass surgery.
Arm Title
Placebo
Arm Type
No Intervention
Arm Description
Research participants will be randomized to not receive intervention in the days prior to coronary artery bypass graft surgery.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone 45 mg
Other Intervention Name(s)
pioglitazone hydrochloride
Intervention Description
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
Primary Outcome Measure Information:
Title
HDL-S1P change
Description
Change in S1P content of isolated HDL between baseline and after treatment with pioglitazone hydrochloride 45 mg/day
Time Frame
Five days
Secondary Outcome Measure Information:
Title
SPHK1 - internal thoracic artery
Description
Difference in SPHK1 expression in the internal thoracic artery cells determined by western blot between groups
Time Frame
Five days
Title
S1PR1 - saphenous vein
Description
Difference in S1P receptor (S1PR1) expression in saphenous vein endothelial cells determined by western blot between groups
Time Frame
Five days
Title
SPHK1 - aortic artery
Description
Difference in SPHK1 expression in the aortic artery cells determined by western blot between groups;
Time Frame
Five days
Title
SPHK1 - atrial appendage
Description
Difference in SPHK1 expression in the atrial appendage cells determined by western blot between groups;
Time Frame
Five days
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrei Sposito, Professor
Phone
+551935218788
Email
sposito@unicamp.br
First Name & Middle Initial & Last Name or Official Title & Degree
Isabella Bonilha, biomedical
Phone
+551935217959
Email
ibonilha@unicamp.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrei Sposito, Professor
Organizational Affiliation
University of Campinas, Brazil
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Campinas
City
Campinas
State/Province
SP
ZIP/Postal Code
13083-887
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrei C Sposito, MD, PhD
Phone
+551935218788
Email
sposito@unicamp.br
First Name & Middle Initial & Last Name & Degree
Andrei C Sposito, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Role of Pioglitazone in Vascular Transcriptional Remodeling
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