CHORD1 - CHOlesterol Lowering and Residual Risk in Diabetes, Type 1

NYU Langone Health

Summary

This is a prospective, interventional, cohort study, meaning that researchers will follow and observe a group of enrolled study participants over a period of time (one to two months) to gather information and record any developments of the outcomes in question. This study will recruit 125 participants with Type 1 Diabetes (T1D) to: 1. Analyze the effect of reducing the cholesterol levels in the blood on platelet function. (Platelets are small cells in the blood which help form blood clots to slow or stop bleeding and to help wounds heal 2. Analyze the effect of reducing the cholesterol levels in the blood on While Blood Cell (WBC) gene expression, (White Blood Cells are part of the body's immune system which help the body fight infection and other diseases) and 3. Analyze the effect of reducing the cholesterol levels in the blood on vascular or blood vessel function.

Description

Participants will receive weekly injections of PCSK9i (evolocumab) plus daily, oral pills of atorvastatin or ezetimibe for 1 month. Participants will undergo blood draw, and optional vascular studies that include: * Glycocalyx testing (A non-invasive test where a video microscope camera is placed under the tongue to capture images of the movement of red blood cells as they travel through the micro-blood vessels) * PET/CT for vascular imaging - to assess any inflammation of blood vessels and to evaluate increased metabolism in related tissues, and * Endothelial cell collection before choleste…

Eligibility

Age range: 18–89 years
Sex: All
Healthy volunteers: No

Detailed criteria

Inclusion Criteria: 1. Participants with previous diagnosis of T1D (as defined by American Diabetes Association or judgment of physician for at least 1 year) 1. American Diabetes Association Criteria for diagnosis of diabetes (Must meet at least 1 of the following criteria): * i. FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours, OR; * ii. 2-h PG ≥200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water, OR; * iii. A1C ≥6.5% (48 mm…

Interventions

Drug
Evolocumab Cartridge
Injectable PCSK9 inhibitor.
Drug
Atorvastatin Calcium Tablets
HMG-CoA reductase inhibitor for oral use.
Drug
Ezetimibe Tablets
Will only be distributed to patients with statin intolerance; replacement for both Atorvastatin and Evolocumab. Inhibitor of intestinal cholesterol for oral use.
Drug
18F-FDG
Optional procedure. Positron emission tomography (PET) and computed tomography (CT) imaging to assess vascular inflammation and related anatomy requires injection of the PET tracer 18F-FDG. 18F-FDG is an FDA-approved analogue of sugar, routinely used to evaluate elevated metabolism in tissues, including increased metabolism due to inflammatory cells. A standard dose of 7.0 mSv will be administered.
Device
Angiocatheter 20IV
Optional procedure (endothelial cell harvesting). An angiocatheter ≤ 21 gauge will be inserted into a peripheral vein on the upper extremity using aseptic technique. A 0.018in. diameter J-shaped wire (Arrow, Reading, PA) will be then advanced into the angiocatheter, to a distance of 4cm beyond the end of the angiocatheter.

Locations (4)

New York VA Hospital
New York, New York
NYC Health + Hospitals/Bellevue
New York, New York
NYU Langone Health
New York, New York
Mount Sinai School of Medicine
New York, New York