Clinical trial NCT04369664
Conditions: Type 2 Diabetes
Sponsor: NYU Langone Health
Start date: 2020-08-12; Completion date: 2023-10-19
Enrollment: 151 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: 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). arm 2: 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).
Interventions: intervention 1: Statin intervention 2: PCSK9 inhibitor intervention 3: Ezetimibe 10mg
Intervention descriptions: intervention 1: Participants will be given up to 80 mg oral tablets daily for the entire study period preferably at the same time each day. intervention 2: 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. intervention 3: 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.

Protocol documents:
Prot_SAP_000.pdf: 
Official Title: 
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3. 
 Specific Aims  
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4. 
Research Design 
4.1 
Recruitment 
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4.2 
Inclusion/Exclusion Criteria for Diabetes Patients 
 
Inclusion Criteria 
*URXS6XEMHFWVZLWKGLDEHWHV
1. $JH	
2. /'/&!PJGO
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3. $EOHDQGZLOOLQJWRSURYLGHZULWWHQLQIRUPHGFRQVHQWIRUWKHVWXG\
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,QGLYLGXDOVZLWKDQ/'/&!PJGOQRWHGDWDVVHVVPHQWVFUHHQLQJZKRVLJQFRQVHQWDQGWKHQDUHIRXQGWR
KDYHDQ/'/&PJGODWEDVHOLQHZLOOQRWEHH[FOXGHG
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Exclusion Criteria 
1. (VWDEOLVKHGFDUGLRYDVFXODUGLVHDVHRQDQWLWKURPERWLFWKHUDS\
2. 7ULJO\FHULGHV!PJGO
3. 8VHRID3&6.LQKLELWRU
4. 5HFHQWLQIHFWLRQLQWKHSDVWGD\V
5. $Q\KRVSLWDOL]DWLRQLQWKHSDVWGD\V
6. 8VHRI,PPXQRVXSSUHVVLYHWKHUDS\
7. 8VHRIDQ\DQWLWKURPERWLFWKHUDS\
8. 8VHRIDVSLULQ
9. 8VHRI16$,'ZLWKLQWKHSDVWKRXUV
10. 3UHJQDQF\
11. $QHPLDKHPRJORELQJGORUWKURPERF\WRSHQLD3ODWHOHWFRXQWRUWKURPERF\WRVLV3ODWHOHWFRXQW
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12. .QRZQKHPRUUKDJLFGLDWKHVLV
13. &KURQLFNLGQH\GLVHDVH&U&OPOPLQ
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4.3 
Inclusion/Exclusion Criteria for Controls 
 
Inclusion Criteria
*URXS6XEMHFWVZLWKRXWNQRZQGLDEHWHV
1. $JH	 
2. Either: LDL-C >100mg/dl, or Lp(a) > 50 mg/dl
D 3UHYLRXVVFUHHQLQJODEVZLOOEHXVHGIRUHOLJLELOLW\DVVHVVPHQWVFUHHQLQJ
3. $EOHDQGZLOOLQJWRSURYLGHZULWWHQLQIRUPHGFRQVHQWIRUWKHVWXG\
 
,QGLYLGXDOVZLWKDQ/'/&!PJGOQRWHGDWDVVHVVPHQWVFUHHQLQJZKRVLJQFRQVHQWDQGWKHQDUHIRXQGWR
KDYHDQ/'/&PJGODWEDVHOLQHZLOOQRWEHH[FOXGHG
 
Exclusion Criteria
1. 'LDEHWHVW\SHRUW\SH
2. $OORWKHUH[FOXVLRQVDUHLGHQWLFDOWRWKHGLDEHWHVJURXS
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4.4 
 Informed consent 
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4.5 
Methods 
4.5.1 Schedule of assessments 
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Table 1. 
Patient Group  
 
Baseline Visit 
Longitudinal 
Analysis 
Initial Follow-up Visit  
(at 4 weeks +/- 5 days) 
Second Follow-
up Visit (at 7-12 
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1.1.4 Endothelial cell harvesting 
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1.1.5 Genetic Profiling 
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Specific Power Analysis: 
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Statistical Analysis Plan for Platelet Activity Measurements 
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Statistical Analysis Plan for Platelet Transcriptomics 
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11. Safety and Adverse Events 
 
11.1 
Definitions 
 
Unanticipated Problems Involving Risk to Subjects or Others 
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Adverse Event 
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Serious Adverse Event 
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Adverse Event Reporting Period 
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Preexisting Condition 
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General Physical Examination Findings 
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Post-study Adverse Event 
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Abnormal Laboratory Values 
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Hospitalization, Prolonged Hospitalization or Surgery 
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11.2 Recording of Adverse Events 
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For Narrative Reports of Safety Events 
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11.3.1 Investigator reporting: notifying the study sponsor 
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Follow-up report: within 48 hours: 
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Other Reportable events: 
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Deviations from the study protocol 
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Withdrawal of IRB approval 
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11.3.2 Investigator reporting: notifying the IRB 
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Report Promptly, but no later than 5 working days: 
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Unanticipated problems including adverse events that are unexpected and related 
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sources of information, such as product labeling and package inserts.  
± Related to the research procedures: An event is related to the research procedures if in the opinion of 
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procedures.  
± Harmful: either caused harm to subjects or others, or placed them at increased risk 
 
Other Reportable events: 
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Reporting Process 
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12. Data Handling and Record Keeping 
 
12.1 Confidentiality 
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Bibliography  
 
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