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Cholesterol Lowering and Residual Risk in Diabetes, Type 1 (CHORD1)

Primary Purpose

Type 1 Diabetes

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Evolocumab Cartridge
Atorvastatin Calcium Tablets
Ezetimibe Tablets
18F-FDG
Angiocatheter 20IV
J-Wire
GlycoCheck Glycocalyx Measurement Software
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Type 1 Diabetes

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants with previous diagnosis of T1D (as defined by American Diabetes Association or judgment of physician for at least 1 year) 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 mmol/mol), OR; iv. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L), AND; History of T1D (due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency, including latent autoimmune diabetes of adulthood). Autoimmune markers include islet cell autoantibodies and autoantibodies to GAD (glutamic acid decarboxylase, GAD65), insulin, the tyrosine phosphatases islet antigen 2 (IA-2) and IA-2β, and zinc transporter 8, OR; Diagnosis of T1D and confirmed by review of records by 2 separate clinical members of the study team Age ≥ 18 & < 90 LDL-C >100mg/dl Able and willing to provide written informed consent for the study Exclusion Criteria: Established cardiovascular disease on antithrombotic therapy Triglycerides >400mg/dl Use of a PCSK9 inhibitor 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 hemorrhagic diathesis Chronic kidney disease (CrCl < 30ml/min) T2D, monogenic diabetes syndromes, or diabetes in the context of disease of the exocrine pancreas (such as pancreatitis, trauma or pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis)

Sites / Locations

  • New York VA HospitalRecruiting
  • NYC Health + Hospitals/BellevueRecruiting
  • NYU Langone HealthRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

4-Week LDL-Cholesterol (LDL-C)-Reduction Treatment

Arm Description

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. Additional procedures: Blood draws. Optional procedures: Glycocalyx testing, PET/CT, or Endothelial Cell Collection.

Outcomes

Primary Outcome Measures

Change in Monocyte Platelet Aggregation (MPA) from Baseline
Measurement of platelet activity. Assessed via patient blood sample.
Change in Light Transmission Aggregation (LTA) from Baseline
Measurement of platelet activity. Assessed via patient blood sample.

Secondary Outcome Measures

Percent Change in Natural Killer (NK) Cell Population from Baseline
Assessed via patient blood sample.
Percent Change in Dendritic Cell Population from Baseline
Assessed via patient blood sample.
Percent Change in CD8 Cell Population from Baseline
Assessed via patient blood sample.

Full Information

First Posted
November 29, 2022
Last Updated
July 27, 2023
Sponsor
NYU Langone Health
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT05641753
Brief Title
Cholesterol Lowering and Residual Risk in Diabetes, Type 1
Acronym
CHORD1
Official Title
CHORD1 - CHOlesterol Lowering and Residual Risk in Diabetes, Type 1
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 6, 2022 (Actual)
Primary Completion Date
July 1, 2027 (Anticipated)
Study Completion Date
July 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief 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: 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.
Detailed 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
125 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
4-Week LDL-Cholesterol (LDL-C)-Reduction Treatment
Arm Type
Experimental
Arm Description
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. Additional procedures: Blood draws. Optional procedures: Glycocalyx testing, PET/CT, or Endothelial Cell Collection.
Intervention Type
Drug
Intervention Name(s)
Evolocumab Cartridge
Other Intervention Name(s)
REPATHA
Intervention Description
Injectable PCSK9 inhibitor.
Intervention Type
Drug
Intervention Name(s)
Atorvastatin Calcium Tablets
Other Intervention Name(s)
LIPITOR
Intervention Description
HMG-CoA reductase inhibitor for oral use.
Intervention Type
Drug
Intervention Name(s)
Ezetimibe Tablets
Other Intervention Name(s)
ZETIA
Intervention Description
Will only be distributed to patients with statin intolerance; replacement for both Atorvastatin and Evolocumab. Inhibitor of intestinal cholesterol for oral use.
Intervention Type
Drug
Intervention Name(s)
18F-FDG
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Angiocatheter 20IV
Other Intervention Name(s)
BD Insyte Autoguard
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
J-Wire
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
GlycoCheck Glycocalyx Measurement Software
Intervention Description
Optional procedure (assessment of vascular function). Video microscope developed by GlycoCheck.
Primary Outcome Measure Information:
Title
Change in Monocyte Platelet Aggregation (MPA) from Baseline
Description
Measurement of platelet activity. Assessed via patient blood sample.
Time Frame
Baseline, Week 4
Title
Change in Light Transmission Aggregation (LTA) from Baseline
Description
Measurement of platelet activity. Assessed via patient blood sample.
Time Frame
Baseline, Week 4
Secondary Outcome Measure Information:
Title
Percent Change in Natural Killer (NK) Cell Population from Baseline
Description
Assessed via patient blood sample.
Time Frame
Baseline, Week 4
Title
Percent Change in Dendritic Cell Population from Baseline
Description
Assessed via patient blood sample.
Time Frame
Baseline, Week 4
Title
Percent Change in CD8 Cell Population from Baseline
Description
Assessed via patient blood sample.
Time Frame
Baseline, Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants with previous diagnosis of T1D (as defined by American Diabetes Association or judgment of physician for at least 1 year) 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 mmol/mol), OR; iv. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L), AND; History of T1D (due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency, including latent autoimmune diabetes of adulthood). Autoimmune markers include islet cell autoantibodies and autoantibodies to GAD (glutamic acid decarboxylase, GAD65), insulin, the tyrosine phosphatases islet antigen 2 (IA-2) and IA-2β, and zinc transporter 8, OR; Diagnosis of T1D and confirmed by review of records by 2 separate clinical members of the study team Age ≥ 18 & < 90 LDL-C >100mg/dl Able and willing to provide written informed consent for the study Exclusion Criteria: Established cardiovascular disease on antithrombotic therapy Triglycerides >400mg/dl Use of a PCSK9 inhibitor 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 hemorrhagic diathesis Chronic kidney disease (CrCl < 30ml/min) T2D, monogenic diabetes syndromes, or diabetes in the context of disease of the exocrine pancreas (such as pancreatitis, trauma or pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ira Goldberg, MD
Phone
646-501-0589
Email
Ira.Goldberg@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ira Goldberg, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York VA Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10010
Country
United States
Individual Site Status
Recruiting
Facility Name
NYC Health + Hospitals/Bellevue
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All of the individual participant data collected during the trial, after deidentification, will be shared upon reasonable request beginning immediately following publication provided the researchers who provide a methodologically sound proposal for use of the data execute a data use agreement with NYU Langone Health. Requests should be directed to Ira.Goldberg@nyulangone.org. The protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code will be made available on Clinicaltrials.gov.
IPD Sharing Time Frame
Immediately following publication. No end date.
IPD Sharing Access Criteria
Researchers who provide a methodologically sound proposal will have access to the data upon reasonable request. Requests should be directed to Ira.Goldberg@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Learn more about this trial

Cholesterol Lowering and Residual Risk in Diabetes, Type 1

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