The Effects of Tirzepatide on Coronary Plaque Lipid Content and Myocardial Microvascular Function in Overweight and Obese People With Coronary Disease - The IDEAL-COR Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 124
- 试验地点
- 3
- 主要终点
- Lipid core burden index
研究概览
简要总结
The objective of this study is to investigate, as a proof-of-principle, long-term (52 weeks) effects of tirzepatide once-weekly vs. placebo on changes in coronary plaque composition and progression (assessed by NIRS), plaque burden (assessed by IVUS) and microvascular function (assessed by invasively measured CFR) in overweight and obese individuals with stable coronary artery disease (CAD). In addition, the objective of a baseline cross-sectional sub-study is to explore potential metabolic and cardiovascular (CV) predictors for high arteriosclerotic plaque burden in overweight and obese individuals and to establish a cohort for future research projects.
详细描述
The anti-atherogenic effect of tirzepatide has been studied in preclinical studies and seems to involve mechanisms related to a reduction in vascular inflammation and lipid accumulation. Any direct anti-atherogenic effect of tirzepatide may potentially reduce the incidence of major cardiovascular endpoints in individuals with overweight or obesity. As a proof of principle, it would be of scientific and clinical interest to explore the anti-atherogenic effect of tirzepatide in humans. IVUS-NIRS imaging is uniquely suited for this purpose, as it makes it possible to detect changes in not only atheroma burden by IVUS but also to detect progression within the plaques in the lipidic/necrotic core component by NIRS. LCBItotal allows for consecutive detection of small changes in the same individual, which is pivotal to explore the supposed antiatherogenic mechanism of tirzepatide with enough statistical power.
The investigators hypothesize that once-weekly sc. tirzepatide can reduce coronary lipid accumulation in the arterial wall and the progression of atheromatosis in individuals with overweight or obesity and established high-risk atherosclerosis. The investigators aim to investigate this hypothesis in a proof-of-principle study by investigating the change in coronary plaque composition in individuals with overweight or obesity and coronary artery disease (CAD) with high-risk characteristics by NIRS imaging randomised to 52-week treatment with tirzepatide or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed written consent
- •BMI equal to or above 27 kg/m2
- •Age 18 years or older
- •Referred to coronary angiogram (CAG) due to stable angina
- •Coronary atheromatosis by angiography (obstructive or non-obstructive)
- •LCBI4mm >200 by NIRS in a vessel not subjected to coronary intervention
排除标准
- •History of diabetes or HbA1c ≥48 mmol/mol (6.5%) at baseline
- •Treatment with Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA)
- •History of coronary artery bypass surgery (CABG)
- •Planned CV intervention (including percutaneous coronary intervention, cardiac surgery or transcatheter valve intervention) at time of randomisation
- •History of heart failure New York Heart Association (NYHA) class III or IV
- •Left ventricular ejection fraction (LVEF) ≤35%
- •eGFR <30 ml/min/1.53 m2
- •History of pancreatitis or plasma amylase >2 times upper normal limit
- •Impaired hepatic function at baseline (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of normal)
- •Pregnancy, planned pregnancy or breastfeeding
- •Family or history of multiple endocrine neoplasia (MEN) type 2 or familial medullary thyroid carcinoma (FMTC)
- •Hypersensitivity to the active substance (Tirzepatide) or to any of the excipients
- •Left main stenosis (≥50% diameter or haemodynamically significant)
- •Chronic total occlusion of any major coronary vessel
- •Multi-vessel disease or complex anatomy potentially requiring coronary bypass surgery
- •Coronary anatomy or pathology precluding the safe performance of intravascular imaging in all major coronary arteries not subjected to intervention
研究组 & 干预措施
Tirzepatide
Tirzepatide is administered sc. once-weekly.
干预措施: Tirzepatide (Drug)
Placebo
Placebo is administered sc. once-weekly.
干预措施: Placebo (Drug)
结局指标
主要结局
Lipid core burden index
时间窗: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Lipid core burden index of the three major coronary vessels (LCBItotal) measured by NIRS imaging.
次要结局
- Percent atheroma volume (PAV)(Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:)
- Number of high-risk coronary lesion(Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:)
- Coronary flow reserve(Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:)
研究者
Tina Vilsbøll
Professor, MD DMSc
Steno Diabetes Center Copenhagen