The Role of Pioglitazone in Vascular Transcriptional Remodeling

NCT05775380 | Unknown Phase 4

• 1 other identifier: PREVALENT
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Myocardial Reperfusion Injury

Outcome Measures

Primary Outcomes (1)

• HDL-S1P change

  Change in S1P content of isolated HDL between baseline and after treatment with pioglitazone hydrochloride 45 mg/day

  Five days

Secondary Outcomes (4)

• SPHK1 - internal thoracic artery

  Five days

• S1PR1 - saphenous vein

  Five days

• SPHK1 - aortic artery

  Five days

• SPHK1 - atrial appendage

  Five days

Study Arms (2)

Pioglitazone

ACTIVE COMPARATOR

Research participants will be randomized to receive pioglitazone hydrochloride 45mg/day for 5 days prior to coronary artery bypass surgery.

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.

Interventions

Pioglitazone 45 mg DRUG

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

Also known as: pioglitazone hydrochloride

Pioglitazone

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Campinas, Brazil: lead

Study Sites (1)

University of Campinas

Campinas, São Paulo, 13083-887, Brazil

RECRUITING

MeSH Terms

Conditions

Myocardial Reperfusion Injury

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Reperfusion Injury; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Andrei Sposito, Professor

  University of Campinas, Brazil

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrei Sposito, Professor

CONTACT

+551935218788; sposito@unicamp.br

Isabella Bonilha, biomedical

CONTACT

+551935217959; ibonilha@unicamp.br

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of cardiology

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: March 20, 2023
• Study Start: June 15, 2023
• Primary Completion: June 28, 2024
• Study Completion: December 22, 2024
• Last Updated: January 12, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)