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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05641753
Recruitment Status : Recruiting
First Posted : December 8, 2022
Last Update Posted : December 8, 2022
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
NYU Langone Health

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:

  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.

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

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

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

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.
Other Name: BD Insyte Autoguard

Device: J-Wire
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.




Primary Outcome Measures :
  1. Change in Monocyte Platelet Aggregation (MPA) from Baseline [ Time Frame: Baseline, Week 4 ]
    Measurement of platelet activity. Assessed via patient blood sample.

  2. Change in Light Transmission Aggregation (LTA) from Baseline [ Time Frame: Baseline, Week 4 ]
    Measurement of platelet activity. Assessed via patient blood sample.


Secondary Outcome Measures :
  1. Percent Change in Natural Killer (NK) Cell Population from Baseline [ Time Frame: Baseline, Week 4 ]
    Assessed via patient blood sample.

  2. Percent Change in Dendritic Cell Population from Baseline [ Time Frame: Baseline, Week 4 ]
    Assessed via patient blood sample.

  3. Percent Change in CD8 Cell Population from Baseline [ Time Frame: Baseline, Week 4 ]
    Assessed via patient blood sample.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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;
    2. 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;
    3. Diagnosis of T1D and confirmed by review of records by 2 separate clinical members of the study team
  2. Age ≥ 18 & < 90
  3. LDL-C >100mg/dl
  4. Able and willing to provide written informed consent for the study

Exclusion Criteria:

  1. Established cardiovascular disease on antithrombotic therapy
  2. Triglycerides >400mg/dl
  3. Use of a PCSK9 inhibitor
  4. Recent infection in the past 30 days
  5. Any hospitalization in the past 30 days
  6. Use of immunosuppressive therapy
  7. Use of any antithrombotic therapy
  8. Use of aspirin
  9. Use of NSAID within the past 72 hours
  10. Pregnancy
  11. Anemia (hemoglobin < 9 g/dl) or thrombocytopenia (platelet count <75), or thrombocytosis (platelet count >600)
  12. A history of hemorrhagic diathesis
  13. Chronic kidney disease (CrCl < 30ml/min)
  14. 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)

Information from the National Library of Medicine

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


Contacts
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Contact: Ira Goldberg, MD 646-501-0589 Ira.Goldberg@nyulangone.org

Locations
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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
Sponsors and Collaborators
NYU Langone Health
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Ira Goldberg, MD NYU Langone Health
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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT05641753    
Other Study ID Numbers: 22-01095
First Posted: December 8, 2022    Key Record Dates
Last Update Posted: December 8, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Immediately following publication. No end date.
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.

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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
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Atorvastatin
Ezetimibe
Evolocumab
Calcium
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors