Effect of Tirzepatide on Progression of Coronary Atherosclerosis Using MDCT

NCT ID: NCT05708859

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-02
• Study Completion Date: 2026-05-31

Brief Summary

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.

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,

Conditions

Type II Diabetes; Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: QUADRUPLE

Study Groups

Tirzepatide

Tirzepatide 15mg Prefilled pen for weekly subcutaneous injection over 52 weeks

Group Type: ACTIVE_COMPARATOR

Tirzepatide

Intervention Type: DRUG

Tirzepatide 15mg Subcutaneous Solution

Placebo

Placebo Prefilled pen (volume matched) for weekly subcutaneous injection over 52 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Volume matched Subcutaneous Solution

Interventions

Tirzepatide

Tirzepatide 15mg Subcutaneous Solution

Intervention Type: DRUG

Placebo

Volume matched Subcutaneous Solution

Intervention Type: DRUG

Other Intervention Names

Mounjaro

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Matthew J. Budoff

OTHER

Sponsor Role: lead

Responsible Party

Matthew J. Budoff

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Matthew A Budoff, MD

Role: PRINCIPAL_INVESTIGATOR

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Locations

Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center (The Lundquist Institute)

Torrance, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sajad Hamal, MS

Role: CONTACT

shamal@lundquist.org

13109749336

Ferdinand Flores, BS

Role: CONTACT

fflores@lundquist.org

13109749333

Facility Contacts

Matthew Budoff, MD

Role: primary

mbudoff@lundquist.org

310-222-4107

Sajad Hamal, MS

Role: backup

shamal@lundquist.org

310-974-9336

Other Identifiers

22915-01

Identifier Type: -

Identifier Source: org_study_id