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Completed

NCT Number: NCT04369664

CHOlesterol Lowering and Residual Risk in Type 2 Diabetes

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.

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Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–89 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

NYU Langone Health

New York, 10016, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Statin

Drug

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

Other names: Atorvastatin

PCSK9 inhibitor

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.

Other names: Evolocumab, Repatha

Ezetimibe 10mg

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.

Other names: Zetia

Primary outcomes

  1. Percent Change in Platelet Activity (MPA) Before and After Cholesterol Reduction

    Time frame: Baseline visit, Follow up visit (4 weeks)

    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. A positive MPA value indicates increased platelet activity, while a negative MPA value indicates decreased platelet activity.

  2. Percent Change in Platelet Activity (LTA) Before and After Cholesterol Reduction

    Time frame: Baseline visit, Follow up visit (4 weeks)

    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. A positive value indicates increased platelet activity, while a negative value indicates decreased platelet activity.

Sponsors and collaborators

Lead sponsor

NYU Langone Health

Other

Registry information

Acronym: CHORD

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Apr 30, 2020
Registry last updated
Oct 17, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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