Coronary Artery Disease Progression in Patients With Prediabetes

NCT ID: NCT02744976

Last Updated: 2022-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2021-09-30

Brief Summary

Prediabetes is a disorder of glucose metabolism that reflects the natural history of progression from normoglycaemia to type 2 diabetes mellitus. Patients with prediabetes have impaired glucose regulation caused by insulin resistance (IR). IR in patients undergoing percutaneous coronary intervention (PCI) is associated with coronary artery remodeling and coronary plaque vulnerability by intravascular ultrasound (IVUS) analysis. In stent restenosis after bare metal and drug-eluting stent implantation more frequently is observed in patients with high fasting-insulin levels and IR. Although IR has a significant role in the progression of atherosclerosis in prediabetic patients, the importance of managing prediabetes is often under-appreciated by clinicians. To date, no pharmacological treatment has been officially approved for prediabetes. According to American Diabetes Association recommendations, metformin is the only drug that could be considered in the treatment of prediabetic patients with a high risk of developing diabetes. Metformin is a safe and inexpensive glucose lowering drug that attenuates mortality and future cardiovascular events in patients with type 2 diabetes as well as the progression of atherosclerosis in non-diabetic animal models. This study was designed to analyze coronary plaque characteristics by iMAP IVUS in patients with and without prediabetes undergoing PCI and to evaluate the impact of metformin treatment on coronary plaque characteristics in prediabetic patients at 24 month follow up.

The study hypothesis is that more pronounced coronary atherosclerosis progression as well as in-stent neointimal hyperplasia will be observed in patients with prediabetes. Metformin treatment attenuates the progression of atherosclerosis in patients with prediabetes.

Detailed Description

Patients undergoing PCI and IVUS pullback for the target vessel will be enrolled in a prospective study. Before PCI and at 24 month follow up fasting blood will be collected for glucose, HbA1c, C peptide, lipid profile assessment. Patients' baseline demographic characteristics, medical history, and procedural data will be collected during the index hospitalization and at 24 month follow up. Patients will be divided in groups according to HbA1c - control group (HbA1c<5.7) and prediabetic patients (HbA1c 5.7-6.4). PCI will be performed in accordance with the guidelines. After successful treatment of the culprit lesion IVUS will be done. Following PCI and IVUS patients with prediabetes will be randomly assigned in groups either receiving metformin at a dose of 2000 mg once daily plus standard lifestyle recommendations or standard lifestyle recommendations only. Intravascular ultrasound analysis will be repeated 24 months after the initial PCI.

Conditions

Coronary Artery Disease; Atherosclerosis; Prediabetic State

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prediabetes, metformin

Patients with HbA1c 5.7-6.4 receiving metformin and lifestyle recommendations

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

In order to minimize gastrointestinal discomfort, metformin treatment will be started with a dose of 500 mg p/o once daily, then gradually increased to 2000 mg p/o once daily for 24 months

Lifestyle recommendations

Intervention Type: BEHAVIORAL

Standard lifestyle recommendations

Prediabetes, lifestyle

Patients with HbA1c 5.7-6.4 receiving lifestyle recommendations

Group Type: ACTIVE_COMPARATOR

Lifestyle recommendations

Intervention Type: BEHAVIORAL

Standard lifestyle recommendations

Interventions

Metformin

In order to minimize gastrointestinal discomfort, metformin treatment will be started with a dose of 500 mg p/o once daily, then gradually increased to 2000 mg p/o once daily for 24 months

Intervention Type: DRUG

Lifestyle recommendations

Standard lifestyle recommendations

Intervention Type: BEHAVIORAL

Other Intervention Names

Glucophage extended release (XR)

Eligibility Criteria

Inclusion Criteria

• age ≥18 and <75 years;
• patients with stable coronary artery disease referred to PCI in an artery suitable for IVUS pullback;
• signed informed consent before PCI.

Exclusion Criteria

• cardiac or non-cardiac illness with life expectancy of less than two years;
• failure to advance the IVUS catheter through the culprit lesion;
• acute coronary syndrome
• congestive heart failure (New York Heart Association (NYHA) classification stage III-IV)
• diabetes mellitus
• chronic kidney disease
• previous PCI in the target vessel
• heavily calcified vessels
• allergy to metformin

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pauls Stradins Clinical University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Karlis Trusinskis

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Pauls Stradins Clinical University hospital

Riga, , Latvia

Countries

Latvia

Other Identifiers

IVUS-0216

Identifier Type: -

Identifier Source: org_study_id