CHOlesterol Lowering and Residual Risk in Type 2 Diabetes

NCT ID: NCT04369664

Last Updated: 2024-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-12
• Study Completion Date: 2023-10-19

Brief Summary

The purpose of this study is to investigate why individuals with type 2 diabetes are at increased risk for heart disease and stroke. This study will investigate risk factors for heart disease and stroke, including platelet (involved in clotting) activity, inflammation, blood vessel wall function, and genetic information (blueprints of your cells), in participants with type 2 diabetes and elevated cholesterol. This study will also include a control group - subjects with elevated cholesterol who do not have diabetes. All participants will be given cholesterol-lowering medicines (PCSK9 inhibitor and statin or ezetimibe) for 1 month with the same risk factors being measured following cholesterol reduction. This study will help understand why individuals with type 2 diabetes are at higher risk for heart disease and stroke before and even after cholesterol reduction.

Detailed Description

As part of this SFRN investigating REPAIR (non-progression of clinical events or regression of atherosclerosis) in T2D, this project will reveal mechanisms behind the platelet mediated increased cardiovascular risk in patients with T2D by focusing on the platelet transcriptome in those with clinical progression and subsequent cardiovascular events versus those without clinical progression. A prospective clinical study will investigate platelet activity and transcriptome before and after significant cholesterol reduction to better understand mechanisms of increased residual risk observed in patients with T2D, even when cholesterol is not elevated. By combining prospective studies on the platelet phenotype in humans with T2D, mechanistic mouse models of diabetes-accelerated atherosclerosis in the Fisher, Basic Project, and the human plaque and genomic data available data from the Giannarelli, Population Project, the investigators believe the research will fill an important and clinically significant gap in the understanding of how diabetes attenuates cardiovascular repair and to identify new treatment and prevention strategies.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Type 2 Diabetes group

All participants with type 2 diabetes will be given cholesterol-lowering medicine (evolocumab (PCSK9 inhibitor) plus atorvastatin (statin) or ezetimibe (zetia)) for 1 month with the same risk factors being measured following cholesterol reduction. They will be asked to undergo blood draw, to receive study medication, and to undergo additional optional vascular health testing including endothelial cell harvesting and glycocalyx (tongue probe).

Group Type: EXPERIMENTAL

Statin

Intervention Type: DRUG

Participants will be given up to 80 mg oral tablets daily for the entire study period preferably at the same time each day.

PCSK9 inhibitor

Intervention Type: DRUG

Participants will receive 2 injections of 140 mg of PCSK9 inhibitor, one will be administered at baseline visit and the other will be self-administered 2 weeks later at home.

Ezetimibe 10mg

Intervention Type: DRUG

Participants who are not able to or not willing to take atorvastatin will be given 10 mg ezetimibe oral tablets daily for the entire study period preferably at the same time each day.

Control group

The participants in the control group are subjects with elevated cholesterol who do not have diabetes. All participants will be given cholesterol-lowering medicines (evolocumab (PCSK9 inhibitor) plus atorvastatin (statin) or ezetimibe (zetia)) for 1 month with the same risk factors being measured following cholesterol reduction. They will be asked to undergo blood draw, to receive study medication, and to undergo additional optional vascular health testing including endothelial cell harvesting and glycocalyx (tongue probe).

Group Type: OTHER

Statin

Intervention Type: DRUG

Participants will be given up to 80 mg oral tablets daily for the entire study period preferably at the same time each day.

PCSK9 inhibitor

Intervention Type: DRUG

Participants will receive 2 injections of 140 mg of PCSK9 inhibitor, one will be administered at baseline visit and the other will be self-administered 2 weeks later at home.

Ezetimibe 10mg

Intervention Type: DRUG

Participants who are not able to or not willing to take atorvastatin will be given 10 mg ezetimibe oral tablets daily for the entire study period preferably at the same time each day.

Interventions

Statin

Participants will be given up to 80 mg oral tablets daily for the entire study period preferably at the same time each day.

Intervention Type: DRUG

PCSK9 inhibitor

Participants will receive 2 injections of 140 mg of PCSK9 inhibitor, one will be administered at baseline visit and the other will be self-administered 2 weeks later at home.

Intervention Type: DRUG

Ezetimibe 10mg

Participants who are not able to or not willing to take atorvastatin will be given 10 mg ezetimibe oral tablets daily for the entire study period preferably at the same time each day.

Intervention Type: DRUG

Other Intervention Names

Atorvastatin; Evolocumab; Repatha; Zetia

Eligibility Criteria

Inclusion Criteria

Subjects with type 2 diabetes:

• Age ≥ 18 & < 90
• LDL-C >100mg/dl
• Able and willing to provide written informed consent for the study

Control subjects without known diabetes:

• Age ≥ 18 & < 90
• LDL-C >100mg/dl or lp(a) >50 mg/dl
• Able and willing to provide written informed consent for the study

Exclusion Criteria

Subjects with type 2 diabetes:

• Established cardiovascular disease on antithrombotic therapy
• Triglycerides >250mg/dl
• Use of a PCSK9 inhibitor
• HbA1c >10%
• Recent infection in the past 30 days
• Any hospitalization in the past 30 days
• Use of Immunosuppressive therapy
• Use of any antithrombotic therapy
• Use of aspirin
• Use of NSAID within the past 72 hours
• Pregnancy
• Anemia (hemoglobin < 9 g/dl) or thrombocytopenia (Platelet count <75), or thrombocytosis (Platelet count >600)
• A history of severe bleeding or bleeding disorders
• Chronic kidney disease (CrCl < 30ml/min)

Control subjects without known diabetes:

• Diabetes (type 1 or type 2)
• All other exclusions are identical to the type 2 diabetes group.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Berger, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

NYU Langone Health

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

19-01964

Identifier Type: -

Identifier Source: org_study_id