Clinical trial NCT04369664: CHOlesterol Lowering and Residual Risk in Type 2 Diabetes
Official title: CHOlesterol Lowering and Residual Risk in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2020-04-30
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percent Change in Platelet Activity (MPA) Before and After Cholesterol Reduction
timeFrame: Baseline visit, Follow up visit (4 weeks)
measure: Percent Change in Platelet Activity (LTA) Before and After Cholesterol Reduction
timeFrame: Baseline visit, Follow up visit (4 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Health
name: Jeffrey Berger, MD
role: PRINCIPAL_INVESTIGATOR
References: