CHOlesterol Lowering and Residual Risk in Type 2 Diabetes
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Statin; PCSK9 inhibitor; Ezetimibe 10mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Participants will be given up to 80 mg oral tablets daily for the entire study period preferably at the same time each day.; 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.; 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 intervention name(s): Atorvastatin; Evolocumab; Repatha; Zetia
Intervention MeSH terms: Atorvastatin; Ezetimibe; Evolocumab; PCSK9 Inhibitors
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment