Cholesterol Lowering and Residual Risk in Diabetes, Type 1

NCT05641753 | Recruiting Phase 4 DMC FDA Drug FDA Device

• 1 other identifier: 22-01095
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 4

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. 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. 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. 3.Analyze the effect of reducing the cholesterol levels in the blood on vascular or blood vessel function.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (2)

• Change in Monocyte Platelet Aggregation (MPA) from Baseline

  Measurement of platelet activity. Assessed via patient blood sample.

  Baseline, Week 4

• Change in Light Transmission Aggregation (LTA) from Baseline

  Measurement of platelet activity. Assessed via patient blood sample.

  Baseline, Week 4

Secondary Outcomes (3)

• Percent Change in Natural Killer (NK) Cell Population from Baseline

  Baseline, Week 4

• Percent Change in Dendritic Cell Population from Baseline

  Baseline, Week 4

• Percent Change in CD8 Cell Population from Baseline

  Baseline, Week 4

Study Arms (1)

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

EXPERIMENTAL

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; Drug: Atorvastatin Calcium Tablets; Drug: Ezetimibe Tablets; Drug: 18F-FDG; Device: Angiocatheter 20IV; Device: J-Wire; Device: GlycoCheck Glycocalyx Measurement Software

Interventions

Evolocumab Cartridge DRUG

Injectable PCSK9 inhibitor.

Also known as: REPATHA

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

Atorvastatin Calcium Tablets DRUG

HMG-CoA reductase inhibitor for oral use.

Also known as: LIPITOR

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

Ezetimibe Tablets DRUG

Will only be distributed to patients with statin intolerance; replacement for both Atorvastatin and Evolocumab. Inhibitor of intestinal cholesterol for oral use.

Also known as: ZETIA

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

18F-FDG DRUG

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.

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

Angiocatheter 20IV DEVICE

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.

Also known as: BD Insyte Autoguard

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

J-Wire DEVICE

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.

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

GlycoCheck Glycocalyx Measurement Software DEVICE

Optional procedure (assessment of vascular function). Video microscope developed by GlycoCheck.

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

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• NYU Langone Health: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

New York VA Hospital

New York, New York, 10010, United States

RECRUITING

NYC Health + Hospitals/Bellevue

New York, New York, 10016, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Mount Sinai School of Medicine

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

evolocumab; Atorvastatin; Ezetimibe; Fluorodeoxyglucose F18

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Azetidines; Azetines; Deoxyglucose; Deoxy Sugars; Carbohydrates

Study Officials

• Ira Goldberg, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ira Goldberg, MD

CONTACT

646-501-0589; Ira.Goldberg@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2022
• First Posted: December 8, 2022
• Study Start: December 6, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (4)