The Effects of Tirzepatide in People With Overweight/Obesity and Coronary Artery Disease (IDEAL-COR)

May 19, 2025 updated by: Tina Vilsbøll

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

124

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Not yet recruiting
        • Rigshospitalet
        • Contact:
        • Principal Investigator:
          • Thomas Engstrøm, DMSci, PhD
      • Gentofte, Denmark, 2900
        • Recruiting
        • Gentofte Hospital
        • Contact:
        • Principal Investigator:
          • Niels Thue Olsen, MD, PhD
      • Herlev, Denmark, 2730

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tirzepatide
Tirzepatide is administered sc. once-weekly.
Drug: Tirzepatide
Investigational drug will be administered as a sc. injection once-weekly.
Other Names:
  • LY3298176
Placebo Comparator: Placebo
Placebo is administered sc. once-weekly.
Drug: Placebo
Placebo containing the same excipients and volume as the active treatment arm but without tirzepatide will be administered as a sc. injection once-weekly.
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lipid core burden index
Time Frame: 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.
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent atheroma volume (PAV)
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Total coronary plaque burden measured by coronary IVUS imaging assessed by 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
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Number of high-risk coronary lesions characterized by maximum lipid core burden index of a 4 mm examined vessel (maxLCBI4mm) ≥325 and plaque burden ≥70%
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Coronary flow reserve
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Coronary flow reserve (CFR) assessed by invasive coronary thermodilution technique during coronary angiogram measures the blood flow in the epicardial arteries and the microvasculature.
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma lipid profile
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Total cholesterol (TC) Triglyceride (TG) High-density lipoprotein cholesterol (HDL-C) LDL-C
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Markers of inflammation
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
High-sensitive C-reactive protein (hsCRP) Interleukin-6 (IL-6)
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Left ventricular systolic and diastolic function assessed by echocardiography:
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Global longitudinal strain (GLS) measured by speckle tracking E/e' measured by tissue-Doppler
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Body composition assessed by DXA scan:
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Regional visceral adipose tissue (VAT) Bone density
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Urine markers of oxidative stress
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
8-oxo-7,8-dihydro2´-deoxyguanosine (8-oxodG) 8-oxo-7,8-dihydroguanosine (8-oxoGuo)
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Myocardial work
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Assessed by pressure-strain loop analysis derived from speckle-tracking echocardiography
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Seattle Angina Questionnaire-7
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Seattle Angina Questionnaire-7 (SAQ-7) measures health status in patients with coronary artery disease. The SAQ-7 generates a summary score (scale 0-100, 100 = full health, 0 = worst health).
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Thromboelastography
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:

Thromboelastography is a viscoelastic hemostatic assay that measures the global viscoelastic properties of whole blood clot formation under low shear stress

The following parameters will be measured:

  • R value = reaction time (min)
  • K = kinetics (min)
  • alpha = angle (degrees)
  • MA = maximum amplitude (mm) Represents the ultimate strength of the fibrin clot; i.e. overall stability of the clot
  • LY30 = amplitude at 30 minutes (%) Percentage decrease in amplitude at 30 minutes post-MA
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
EuroQoL 5-Dimension 5-Level
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
The EuroQoL 5-Dimension 5-Level (EQ-5D-5L) is questionnaire of 5 health dimensions - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression - and includes 5 response categories of no problem, slight problems, moderate problems, severe problems, and extreme problems. The 5 responses give a health state or profile represented by a 5-digit number (for example, 12231) corresponding to response categories reported by patients for successive dimensions, beginning with mobility. Health states are scored to give the EQ-5D-5L index using a scoring algorithm from a value set derived from valuation tasks typically undertaken with general population samples. Index scores range from -0.59 to 1; 1 is the best possible health state.
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Liver stiffness measurement
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Liver Stiffness Measurement (LSM): This measurement is performed using a technology called Fibroscan. It measures the stiffness or hardness of the liver, which correlates with the degree of liver fibrosis (scarring). The result is expressed in kilopascals (kPa). Normal liver stiffness values typically range from 2 to 7 kPa, with higher values indicating more severe fibrosis.
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Controlled Attenuation Parameter
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Controlled Attenuation Parameter (CAP): This measurement is performed using a technology called Fibroscan. This measures the amount of fat in the liver, known as steatosis. The CAP score is expressed in decibels per meter (dB/m) and ranges from 100 to 400 dB/m. Higher CAP scores indicate greater levels of liver fat.
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Homeostatic Model Assessment for Insulin Resistance
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:

Homeostatic model assessment of insulin resistance (HOMA-IR) evaluates systemic insulin resistance. HOMA-IR is calculated using fasting blood glucose and fasting insulin levels. The formula for HOMA-IR is: HOMA-IR = (Fasting Insulin uU/mL * Fasting Glucose mmol/L)/22.5

HOMA-IR values between 0.5 and 1.4 are considered normal. ≥1.9 are indicative of early insulin resistance, and ≥2.9 indicate insulin resistance.
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Fibrosis-4 score
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:

Fibrosis-4 (FIB-4) score is a non-invasive scoring system used to estimate the amount of liver fibrosis in individuals. The score is calculated using the following formula:

FIB-4 = (Age * aspartate aminotransferase level U/L )/(Platelet count 10^9/L * squareroot(alanine aminotransferase level U/L ))

The resulting score helps to stratify patients into different risk categories for liver fibrosis Low risk: FIB-4 under 1.3 Intermediate risk: FIB-4 between 1.3 and 2.67 High risk: FIB-4 above 2.67
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Glycaemic profile
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Glycaemic variability measured by continuous glucose monitoring (CGM) Fasting plasma glucose (FPG) Glycated haemoglobin A1c (HbA1c)
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Change in glycaemic variability
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:

Glycaemic variability measured by continuous glucose monitoring (CGM) refers to the fluctuations in blood glucose levels over time.

The following metrics are used to quantify glycaemic variability:

Standard Deviation (SD): Measures the dispersion of glucose values around the mean.

Coefficient of Variation (CV): The ratio of the standard deviation to the mean glucose level, expressed as a percentage.

Mean Amplitude of Glycemic Excursions (MAGE): Captures the average of the absolute differences between consecutive peaks and nadirs in glucose levels.

Continuous Overlapping Net Glycemic Action (CONGA): Measures the variability of glucose levels over a specified period.
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Change in fasting plasma glucose
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Fasting plasma glucose (FPG)
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Change in glycated haemoglobin A1c
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Glycated haemoglobin A1c (HbA1c)
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Index of microcirculatory resistance
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo
Index of microcirculatory resistance (IMR) assessed by coronary thermodilution technique during coronary angiogram
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo
Resistive Reserve Ratio
Time Frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo
Resistive Reserve Ratio (RRR) assessed by coronary thermodilution technique during coronary angiogram is a measure used to evaluate the vasodilatory capacity of the coronary microvasculature.
Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tina Vilsbøll

Investigators

  • Principal Investigator: Tina Vilsbøll, MD, DMSc, Steno Diabetes Center Copenhagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2024

Primary Completion (Estimated)

March 20, 2027

Study Completion (Estimated)

August 1, 2028

Study Registration Dates

First Submitted

September 4, 2024

First Submitted That Met QC Criteria

September 19, 2024

First Posted (Actual)

September 23, 2024

Study Record Updates

Last Update Posted (Actual)

May 22, 2025

Last Update Submitted That Met QC Criteria

May 19, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-505270-15-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in the clinical trial, after de-identification will be available in accordance with Danish data regulations.

IPD Sharing Time Frame

Data will be available beginning 1 year after the end of the trial and publication of the primary outcomes, and will be available for 24 months.

IPD Sharing Access Criteria

Data will be available to researchers who provide a methodologically sound proposal. Proposals should be directed to Prof. Tina Vilsbøll, MD DMSc, at tina.vilsboell.01@regionh.dk. To gain access, data requestors will need to sign a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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