CHOlesterol Lowering and Residual Risk in Type 2 Diabetes

NCT04369664 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 19-01964
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (2)

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

  Baseline visit, Follow up visit (4 weeks)

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

  Baseline visit, Follow up visit (4 weeks)

Study Arms (2)

Type 2 Diabetes group

EXPERIMENTAL

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).

Drug: Statin; Drug: PCSK9 inhibitor; Drug: Ezetimibe 10mg

Control group

OTHER

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).

Drug: Statin; Drug: PCSK9 inhibitor; Drug: Ezetimibe 10mg

Interventions

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.

Also known as: Atorvastatin

Control group; Type 2 Diabetes group

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.

Also known as: Evolocumab, Repatha

Control group; Type 2 Diabetes group

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.

Also known as: Zetia

Control group; Type 2 Diabetes group

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; evolocumab; Ezetimibe

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Azetidines; Azetines

Results Point of Contact

• Title: Jeffrey Berger, MD
• Organization: NYU Langone Health

jeffrey.berger@nyulangone.org

212-263-4004

Study Officials

• Jeffrey Berger, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 30, 2020
• Study Start: August 12, 2020
• Primary Completion: September 25, 2023
• Study Completion: October 19, 2023
• Last Updated: October 17, 2024
• Results First Posted: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (1)