CHOlesterol Lowering and Residual Risk in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— CHORD  

Official title:

CHOlesterol Lowering and Residual Risk in Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04369664
• Other study ID #: 19-01964
• Status: Completed
• Phase: Phase 4
• Start date: August 12, 2020
• Est. completion date: October 19, 2023

Study information

• Verified date: October 2023
• Source: NYU Langone Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: October 19, 2023
• Est. primary completion date: September 25, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Statin
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
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
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.

Locations

Country	Name	City	State
United States	NYU Langone Health	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
NYU Langone Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in platelet activity (MPA) before and after cholesterol reduction	The difference in platelet activity will be assessed by measuring changes in monocyte-platelet aggregates. Monocyte platelet aggregates (MPA) are a robust marker of platelet activity and inflammatory monocytes. The difference in platelet activity before and after cholesterol reduction will be compared using paired t-test or Wilcoxon signed-rank test. The study will also perform a linear mixed model for the multivariate analysis; the primary outcome will be the change in platelet activity (MPA) before and after cholesterol reduction. All tests will be 2-tailed, and a P <0.05 will be considered as statistically significant.	Baseline visit, Follow up visit (4 weeks)
Primary	Change in platelet activity (LTA) before and after cholesterol reduction	The difference in platelet activity will be assessed by using the light transmission aggregometry test (LTA). Light Transmission Aggregometry [LTA] is frequently undertaken as the first test of platelet function, as a screening test for a bleeding disorder and in addition for monitoring of anti-platelet drugs using platelet rich plasma (PRP). The difference in platelet activity before and after cholesterol reduction will be compared using paired t-test or Wilcoxon signed-rank test. We will also perform a linear mixed model for the multivariate analysis; the primary outcome will be the change in platelet activity (LTA) before and after cholesterol reduction. All tests will be 2-tailed, and a P <0.05 will be considered as statistically significant.	Follow up visit (4 weeks)