Effect of Tirzepatide on Progression of Coronary Atherosclerosis Using MDCT (T-PLAQUE)

A multi-center, randomized, double-blind, placebo-controlled, parallel-group phase IV Study evaluating the effects of tirzepatide on atherosclerotic plaque progression assessed by coronary computed tomography angiography (CCTA) in participants with a diagnosis of type II Diabetes (T2DM) and atherosclerosis.

Study Overview

• Status: Recruiting
• Conditions: Atherosclerosis; Type II Diabetes
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo

Detailed Description

This is a multi-center study in which 120 male and female participants who meet the eligibility criteria will be randomized. Study will assess changes in coronary atheroma volume comparing tirzepatide 15 mg/week plus Standard of Care (SOC), as compared to placebo plus SOC. Potential eligible participants may be prescreened for eligibility prior to the screening visit and must have a diagnosis of atherosclerosis (as assessed by >10% atheroma on CCTA) and T2DM.

Patients must be on a stable medical regiment (>4 weeks on statin therapy and diabetes medications) and undergo screening CCTA to demonstrate coronary plaque. Participant eligibility will be assessed by the Imaging Core Lab.

If the participant meets all entry criteria during baseline visit, then consenting participants will be randomized 1:1 to receive tirzepatide on top of standard of care for treatment period of 12 months. Participants will be asked to maintain stable doses of statins and diabetes medications. Persistent hyperglycemia will be treated by primary physician or endocrinologist,

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sajad Hamal, MS; Phone Number: 13109749336; Email: shamal@lundquist.org
• Study Contact Backup: Name: Ferdinand Flores, BS; Phone Number: 13109749333; Email: fflores@lundquist.org

Study Locations

• United States
  • California
    • Torrance, California, United States, 90502
      • Recruiting
      • Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center (The Lundquist Institute)
      • Contact: Matthew Budoff, MD; Phone Number: 310-222-4107; Email: mbudoff@lundquist.org
      • Contact: Sajad Hamal, MS; Phone Number: 310-974-9336; Email: shamal@lundquist.org
      • Principal Investigator: Matthew J Budoff, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female 40 years to 80 years of age at signing of informed consent
2. Type 2 DM of minimum 5 years duration with HbA1c ≥7.0% to ≤10.5%
3. Body mass index (BMI) ≥25 kilograms per meter squared (kg/m²)
4. Presence of two discrete coronary artery plaques with visual diameter stenosis >20% on CCTA
5. At the baseline visit, participants must be on a stable (>4 weeks) regiment of diabetes medications.
6. Patients using oral hormonal contraceptives must switch to a non-oral contraceptive method, or add a barrier method of contraception for 4 weeks after initiation and for 4 weeks after each dose escalation

Exclusion Criteria:

1. Have had a major cardiovascular event within the last 60 days
2. Have type 1 diabetes mellitus
3. Current use of GLP1-RA
4. Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the last 6 months
5. Are currently planning treatment for diabetic retinopathy and/or macular edema
6. Have history of, or currently planning a coronary, carotid, or peripheral artery revascularization (ie - stent, bypass)
7. Have a history of pancreatitis
8. Have a history of ketoacidosis or hyperosmolar state/coma
9. Have a known clinically significant gastric emptying abnormality, have undergone or currently planning any gastric outlet obstruction, or have undergone or currently planning any gastric bypass (bariatric) surgery or restrictive bariatric surgery
10. Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years
11. Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
12. Have had a blood transfusion or severe blood loss within 90 days prior to screening or have known hematological conditions that may interfere with HbA1c measurement
13. Planned or Prior Bypass surgery
14. Contradiction for CCTA (e.g. serious allergic reaction to the contrast dye) or CCTA not meeting entry standards after two attempts during the Baseline CCTA visit as assessed by the imaging core lab.
15. Uncontrolled severe hypertension: systolic blood pressure > 180 mmHg or diastolic BP > 100 mm Hg prior to randomization (assessed at the screening visit) despite antihypertensive therapy
16. Heart Failure NYHA Class III or IV at the screening visit
17. Renal insufficiency (eGFR <40 ml/min/1.73m2) as measured by the Modification of Diet in Renal Disease (MDRD) formula at the screening visit.
18. Hospitalization for major cardiovascular event including heart failure in the past 2 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tirzepatide; Tirzepatide 15mg Prefilled pen for weekly subcutaneous injection over 52 weeks	Drug: Tirzepatide; Tirzepatide 15mg Subcutaneous Solution; Other Names: Mounjaro
Placebo Comparator: Placebo; Placebo Prefilled pen (volume matched) for weekly subcutaneous injection over 52 weeks	Drug: Placebo; Volume matched Subcutaneous Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of total non-calcified coronary plaque volume	Reduction of total non-calcified coronary plaque volume from baseline (start of the study) till the final visit will be measured using Coronary Computed Tomography Angiography (CCTA).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of low attenuation plaque volume	Reduction change in low attenuation plaque volume from baseline (start of the study) till the final visit will be measured using Coronary Computed Tomography Angiography (CCTA)	12 months
Reduction of total plaque volume, fibrous, lipid-rich and calcified plaque volumes using CCTA	Reduction change of total plaque volume, fibrous, lipid-rich and calcified plaque volumes will be compared between baseline and at the end of the study.	12 months
Change in HgA1c lab values in the blood.	Change in HgA1c lab values in the blood will be compared between baseline and at the end of the study.	12 months

Collaborators and Investigators

• Sponsor: Matthew J. Budoff
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Matthew A Budoff, MD, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): February 1, 2023

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 10, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Diabetes Mellitus; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Diabetes Mellitus, Type 2; Atherosclerosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 22915-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes