A Phase 4 interventional study of Tirzepatide and Placebo in Coronary Artery Disease, Coronary Microvascular Dysfunction and Overweight or Obesity, sponsored by Tina Vilsbøll. Recruiting at 3 sites in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-22.
Sponsored by Tina Vilsbøll · Phase 4, Interventional, and Treatment
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.
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.
4,857 studies on the registry are indexed under Coronary Artery Disease; 890 are open to participants now.
This study's planned enrollment of 124 is close to the median of 124 across 3,006 interventional studies indexed under Coronary Artery Disease.
Browse Coronary Artery Disease studies →This is the only study on the registry with Tina Vilsbøll as lead sponsor.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Tirzepatide is administered sc. once-weekly.
Drug: Tirzepatide
Placebo is administered sc. once-weekly.
Drug: Placebo
Investigational drug will be administered as a sc. injection once-weekly.
Also known as: LY3298176
Placebo containing the same excipients and volume as the active treatment arm but without tirzepatide will be administered as a sc. injection once-weekly.
Also known as: Saline
Lipid core burden index
Lipid core burden index of the three major coronary vessels (LCBItotal) measured by NIRS imaging.
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Percent atheroma volume (PAV)
Total coronary plaque burden measured by coronary IVUS imaging assessed by Percent atheroma volume (PAV)
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Number of high-risk coronary lesion
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%
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Coronary flow reserve
Coronary flow reserve (CFR) assessed by invasive coronary thermodilution technique during coronary angiogram measures the blood flow in the epicardial arteries and the microvasculature.
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Plasma lipid profile
Total cholesterol (TC) Triglyceride (TG) High-density lipoprotein cholesterol (HDL-C) LDL-C
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Markers of inflammation
High-sensitive C-reactive protein (hsCRP) Interleukin-6 (IL-6)
Time frame: 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:
Global longitudinal strain (GLS) measured by speckle tracking E/e' measured by tissue-Doppler
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Body composition assessed by DXA scan:
Regional visceral adipose tissue (VAT) Bone density
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Urine markers of oxidative stress
8-oxo-7,8-dihydro2´-deoxyguanosine (8-oxodG) 8-oxo-7,8-dihydroguanosine (8-oxoGuo)
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Myocardial work
Assessed by pressure-strain loop analysis derived from speckle-tracking echocardiography
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Seattle Angina Questionnaire-7
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).
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Thromboelastography
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
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
EuroQoL 5-Dimension 5-Level
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.
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Liver stiffness measurement
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.
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Controlled Attenuation Parameter
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.
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Homeostatic Model Assessment for Insulin Resistance
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.
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Fibrosis-4 score
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
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Glycaemic profile
Glycaemic variability measured by continuous glucose monitoring (CGM) Fasting plasma glucose (FPG) Glycated haemoglobin A1c (HbA1c)
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Change in glycaemic variability
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.
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Change in fasting plasma glucose
Fasting plasma glucose (FPG)
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Change in glycated haemoglobin A1c
Glycated haemoglobin A1c (HbA1c)
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo:
Index of microcirculatory resistance
Index of microcirculatory resistance (IMR) assessed by coronary thermodilution technique during coronary angiogram
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo
Resistive Reserve Ratio
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.
Time frame: Between-group difference in change from baseline to week 52 in participants treated with tirzepatide vs placebo
Plan to share: Yes — Individual participant data that underlie the results reported in the clinical trial, after de-identification will be available in accordance with Danish data regulations.
Supporting information: Study protocol, Statistical analysis plan
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.
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.
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Studies of the drug tested here: Tirzepatide