- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04369664
CHOlesterol Lowering and Residual Risk in Type 2 Diabetes (CHORD)
October 24, 2023 updated by: NYU Langone Health
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
151
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Jeffrey Berger, MD
- Phone Number: 212-263-4004
- Email: jeffrey.berger@nyulangone.org
Study Contact Backup
- Name: Maja Fadzan
- Phone Number: 347-964-3380
- Email: maja.fadzan@nyulangone.org
Study Locations
-
-
New York
-
New York, New York, United States, 10016
- NYU Langone Health
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 89 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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).
|
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:
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:
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:
|
Other: 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).
|
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:
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:
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline visit, Follow up visit (4 weeks)
|
Change in platelet activity (LTA) before and after cholesterol reduction
Time Frame: 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.
|
Follow up visit (4 weeks)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Jeffrey Berger, MD, NYU Langone Health
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 12, 2020
Primary Completion (Actual)
September 25, 2023
Study Completion (Actual)
October 19, 2023
Study Registration Dates
First Submitted
April 27, 2020
First Submitted That Met QC Criteria
April 28, 2020
First Posted (Actual)
April 30, 2020
Study Record Updates
Last Update Posted (Actual)
October 26, 2023
Last Update Submitted That Met QC Criteria
October 24, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Protease Inhibitors
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Serine Proteinase Inhibitors
- Atorvastatin
- Evolocumab
- Ezetimibe
- PCSK9 Inhibitors
Other Study ID Numbers
- 19-01964
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
IPD Sharing Time Frame
Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
IPD Sharing Access Criteria
The investigator who proposed to use the data and upon reasonable request.
Requests should be directed to jeffrey.berger@nyulangone.org.
To gain access, data requestors will need to sign a data access agreement.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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