Coronary Artery Disease Progression in Patients With Prediabetes

NCT02744976 | Completed Phase 4

• 1 other identifier: IVUS-0216
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease; Atherosclerosis; Prediabetic State

Keywords

Coronary artery disease; Atherosclerosis; Prediabetes; Intravascular ultrasound; Insulin resistance; Percutaneous coronary intervention; Metformin

Outcome Measures

Primary Outcomes (1)

• Percentage plaque volume change over 24 months

  Changes in plaque volume in 24 months

  24 months

Secondary Outcomes (4)

• Culprit lesion in-stent restenosis

  24 months

• Plaque tissue component percentage change over 24 months

  24 months

• Correlation of glycemic parameters with plaque characteristics

  At index hospitalization and follow up (24 months)

• Plaque volume change in metformin vs non-metformin treated patients over 24 months

  24 months

Study Arms (2)

Prediabetes, metformin

EXPERIMENTAL

Patients with HbA1c 5.7-6.4 receiving metformin and lifestyle recommendations

Drug: Metformin; Behavioral: Lifestyle recommendations

Prediabetes, lifestyle

ACTIVE COMPARATOR

Patients with HbA1c 5.7-6.4 receiving lifestyle recommendations

Behavioral: Lifestyle recommendations

Interventions

Metformin 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

Also known as: Glucophage extended release (XR)

Prediabetes, metformin

Lifestyle recommendations BEHAVIORAL

Standard lifestyle recommendations

Prediabetes, lifestyle; Prediabetes, metformin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pauls Stradins Clinical University Hospital: lead

Study Sites (1)

Pauls Stradins Clinical University hospital

Riga, Latvia

Location

MeSH Terms

Conditions

Coronary Artery Disease; Atherosclerosis; Prediabetic State; Insulin Resistance

Interventions

Metformin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 15, 2016
• First Posted: April 20, 2016
• Study Start: February 1, 2016
• Primary Completion: July 31, 2019
• Study Completion: September 1, 2021
• Last Updated: April 22, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

LA (1)