Cholesterol Lowering and Residual Risk in Diabetes, Type 1

NCT ID: NCT05641753

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-06

Study Completion Date

2027-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Type 1 Diabetes

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Evolocumab Cartridge

Intervention Type DRUG

Injectable PCSK9 inhibitor.

Atorvastatin Calcium Tablets

Intervention Type DRUG

HMG-CoA reductase inhibitor for oral use.

Ezetimibe Tablets

Intervention Type DRUG

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

18F-FDG

Intervention Type 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.

Angiocatheter 20IV

Intervention Type 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.

J-Wire

Intervention Type 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.

GlycoCheck Glycocalyx Measurement Software

Intervention Type DEVICE

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

Interventions

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Evolocumab Cartridge

Injectable PCSK9 inhibitor.

Intervention Type DRUG

Atorvastatin Calcium Tablets

HMG-CoA reductase inhibitor for oral use.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type 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.

Intervention Type DEVICE

GlycoCheck Glycocalyx Measurement Software

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

Intervention Type DEVICE

Other Intervention Names

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REPATHA LIPITOR ZETIA BD Insyte Autoguard

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

NYU Langone Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ira Goldberg, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

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New York VA Hospital

New York, New York, United States

Site Status RECRUITING

NYC Health + Hospitals/Bellevue

New York, New York, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Mount Sinai School of Medicine

New York, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ira Goldberg, MD

Role: CONTACT

Phone: 646-501-0589

Email: [email protected]

Other Identifiers

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22-01095

Identifier Type: -

Identifier Source: org_study_id