Cholesterol Lowering and Residual Risk in Diabetes, Type 1 (CHORD1)
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|ClinicalTrials.gov Identifier: NCT05641753|
Recruitment Status : Recruiting
First Posted : December 8, 2022
Last Update Posted : December 8, 2022
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:
- 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
- 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
- Analyze the effect of reducing the cholesterol levels in the blood on vascular or blood vessel function.
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes||Drug: Evolocumab Cartridge Drug: Atorvastatin Calcium Tablets Drug: Ezetimibe Tablets Drug: 18F-FDG Device: Angiocatheter 20IV Device: J-Wire Device: GlycoCheck Glycocalyx Measurement Software||Phase 4|
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 cholesterol reduction and 1-month after cholesterol reduction to measure any genetic changes in in the endothelial cells before and after collection
Glycemic Variability (GV), the amount one's blood sugar changes throughout the day, will be analyzed from continuous glucose monitoring (CGM) data.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||125 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||CHORD1 - CHOlesterol Lowering and Residual Risk in Diabetes, Type 1|
|Actual Study Start Date :||November 16, 2022|
|Estimated Primary Completion Date :||January 2027|
|Estimated Study Completion Date :||January 2027|
Experimental: 4-Week LDL-Cholesterol (LDL-C)-Reduction Treatment
Treatment consists of: Evolocumab (140 mg; 2 injections, one administered at baseline visit and another self-administered 2 weeks later), and; Atorvastatin (up to 80mg dose; 1 tab per day for 30 days, starting at baseline visit post-assessment). Participants with statin intolerance will be provided with a 1-month supply of ezetimibe 10 mg to replace Evolocumab and Atorvastatin.
Drug: Evolocumab Cartridge
Injectable PCSK9 inhibitor.
Other Name: REPATHA
Drug: Atorvastatin Calcium Tablets
HMG-CoA reductase inhibitor for oral use.
Other Name: LIPITOR
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.
Other Name: ZETIA
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.
Other Name: BD Insyte Autoguard
Optional procedure (endothelial cell harvesting). Either a 0.021in. diameter J-shaped wire (Daig, Minnetonka, MN) or a 0.018in. diameter J-shaped wire (Arrow, Reading, PA) will be used.
Device: GlycoCheck Glycocalyx Measurement Software
Optional procedure (assessment of vascular function). Video microscope developed by GlycoCheck.
- Change in Monocyte Platelet Aggregation (MPA) from Baseline [ Time Frame: Baseline, Week 4 ]Measurement of platelet activity. Assessed via patient blood sample.
- Change in Light Transmission Aggregation (LTA) from Baseline [ Time Frame: Baseline, Week 4 ]Measurement of platelet activity. Assessed via patient blood sample.
- Percent Change in Natural Killer (NK) Cell Population from Baseline [ Time Frame: Baseline, Week 4 ]Assessed via patient blood sample.
- Percent Change in Dendritic Cell Population from Baseline [ Time Frame: Baseline, Week 4 ]Assessed via patient blood sample.
- Percent Change in CD8 Cell Population from Baseline [ Time Frame: Baseline, Week 4 ]Assessed via patient blood sample.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05641753
|Contact: Ira Goldberg, MD||646-501-0589||Ira.Goldberg@nyulangone.org|
|United States, New York|
|New York VA Hospital||Recruiting|
|New York, New York, United States, 10010|
|NYC Health + Hospitals/Bellevue||Recruiting|
|New York, New York, United States, 10016|
|NYU Langone Health||Recruiting|
|New York, New York, United States, 10016|
|Principal Investigator:||Ira Goldberg, MD||NYU Langone Health|