Lowering cholesterol to assess health impacts in Type 1 Diabetes

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

This study is testing whether lowering cholesterol with injections and pills can improve health markers in people with Type 1 Diabetes.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 125 (estimated)
• Ages: 18 Years to 89 Years
• Sex: All
• Sponsor: NYU Langone Health (other)
• Drugs / interventions: evolocumab
• Locations: 4 sites (New York, New York and 3 other locations)
• Trial ID: NCT05641753 on ClinicalTrials.gov

What this trial studies

This interventional study will recruit 125 participants with Type 1 Diabetes to evaluate the effects of cholesterol reduction on various health parameters. Participants will receive weekly injections of evolocumab along with daily oral atorvastatin or ezetimibe for one month. The study will analyze changes in platelet function, white blood cell gene expression, and vascular function through blood draws and optional vascular imaging tests. Continuous glucose monitoring will also be utilized to assess glycemic variability during the study period.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with Type 1 Diabetes for at least one year.

Not a fit: Patients without a diagnosis of Type 1 Diabetes or those with other significant health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved cardiovascular health and better management of Type 1 Diabetes through cholesterol reduction.

How similar studies have performed: Other studies have shown promising results in cholesterol management and its effects on diabetes-related complications, suggesting this approach may be beneficial.

Eligibility 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)

Where this trial is running

New York, New York and 3 other locations

• New York VA Hospital — New York, New York, United States (RECRUITING)
• NYC Health + Hospitals/Bellevue — New York, New York, United States (RECRUITING)
• NYU Langone Health — New York, New York, United States (RECRUITING)
• Mount Sinai School of Medicine — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Ira Goldberg, MD — NYU Langone Health
• Study coordinator: Ira Goldberg, MD

Conditions: Type 1 Diabetes