Cholesterol-Lowering Drugs for Type 1 Diabetes

(CHORD1 Trial)

Recruiting at 3 trial locations

Overseen By Zahi Fayad

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: NYU Langone Health

Must not be taking: PCSK9 inhibitors, Antithrombotics, Aspirin, NSAIDs

Disqualifiers: Cardiovascular disease, Recent infection, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how lowering cholesterol affects people with Type 1 Diabetes, focusing on blood cell and blood vessel function. Participants will receive treatments such as daily atorvastatin tablets (Lipitor) or evolocumab injections (Repatha) to assess the impact on their health. The study seeks individuals who have had Type 1 Diabetes for at least a year and have LDL cholesterol levels above 100 mg/dL. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, helping researchers understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain medications like antithrombotic therapy, aspirin, NSAIDs, or PCSK9 inhibitors.

What is the safety track record for these treatments?

A previous study found that atorvastatin, a cholesterol-lowering drug, carries a very low risk of causing serious muscle injury, affecting less than 0.1% of users. It also posed a very rare chance of causing serious liver damage, at about 0.001%. However, some research suggests atorvastatin might slightly raise blood sugar levels, which could concern people with diabetes.

Evolocumab, another cholesterol-lowering drug, has been shown in many studies to be safe and well-tolerated, even for people with diabetes and those who cannot take statins. Its safety has been consistent in over 27,000 patients.

Ezetimibe, often used with statins, has not been linked to a higher risk of developing diabetes in studies, suggesting it is safe for people with diabetes.

Overall, these treatments have been shown to be safe for many people, including those with diabetes. However, everyone is different, and discussing any concerns with a healthcare provider before starting any new medication is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because they offer new ways to lower cholesterol in people with Type 1 diabetes, a group often left out of traditional cholesterol management strategies. Unlike standard options like statins, Evolocumab is a PCSK9 inhibitor that works by helping the liver remove more LDL cholesterol from the blood, potentially offering more effective lipid-lowering in those who may not respond well to statins alone. Additionally, Ezetimibe works differently by blocking the absorption of cholesterol in the intestines, providing an alternative for those who can't tolerate statins. This combination of treatments could offer more tailored and effective cholesterol management for individuals with Type 1 diabetes.

What evidence suggests that this trial's treatments could be effective for Type 1 Diabetes?

Research has shown that atorvastatin, one of the treatments available in this trial, effectively lowers LDL cholesterol, often called "bad" cholesterol, in people with Type 1 Diabetes. This reduction can help decrease the risk of heart problems such as heart attacks and strokes. Evolocumab, another drug option in this trial, also significantly lowers LDL cholesterol, with some studies indicating it can reduce levels by more than 50%. For participants with statin intolerance, ezetimibe is provided and can further lower LDL cholesterol by 15–22% when combined with statins. Overall, evidence strongly supports these treatments for lowering cholesterol and improving heart health. ^{1 3 6 7 8}

Who Is on the Research Team?

Ira Goldberg, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 89 with Type 1 Diabetes and LDL cholesterol over 100mg/dl. They must have a confirmed diagnosis of T1D, not be pregnant, and cannot have been hospitalized or had an infection in the last month. Participants should not be on aspirin, NSAIDs within the past three days, immunosuppressives, antithrombotics, or PCSK9 inhibitors.

Inclusion Criteria

I have been diagnosed with diabetes based on blood sugar or A1C levels.

Your LDL cholesterol is higher than 100 milligrams per deciliter.

You have a history of type 1 diabetes, including a specific type called latent autoimmune diabetes of adulthood.

Exclusion Criteria

I have taken NSAID medication in the last 3 days.

You have low hemoglobin or platelet levels in your blood.

I am on medication to prevent blood clots due to heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly injections of PCSK9i (evolocumab) and daily oral pills of atorvastatin or ezetimibe for 1 month

4 weeks

1 visit (in-person) at baseline, 1 self-administered injection at 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin Calcium Tablets
• Evolocumab Cartridge
• Ezetimibe Tablets

Trial Overview

The study tests how lowering cholesterol affects platelet function (which helps blood clot), White Blood Cell gene expression (important for fighting infections), and blood vessel function in people with Type 1 Diabetes using Evolocumab Cartridge combined with Atorvastatin Calcium Tablets or Ezetimibe Tablets.

How Is the Trial Designed?

Group I: 4-Week LDL-Cholesterol (LDL-C)-Reduction Treatment Experimental Treatment 7 Interventions

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.

Atorvastatin Calcium Tablets is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease
• Homozygous familial hypercholesterolemia

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a 12-week phase 3 study involving 981 patients with type 2 diabetes and high cholesterol, evolocumab significantly reduced LDL cholesterol levels by up to 74.9% when combined with atorvastatin, compared to placebo.

Evolocumab was well tolerated, showing a similar incidence of adverse events as placebo, and did not adversely affect blood sugar levels, indicating it is a safe option for lipid management in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Primary results of the BERSON clinical trial. Lorenzatti, AJ., Eliaschewitz, FG., Chen, Y., et al.[2021]

Ezetimibe is a selective cholesterol absorption inhibitor that effectively blocks the absorption of dietary and biliary cholesterol in the small intestine without affecting the absorption of bile acids, fatty acids, or fat-soluble vitamins.

It is approved for treating primary hypercholesterolemia, either alone or with statins, and is also used for homozygous familial hypercholesterolemia and homozygous sitosterolemia, highlighting its versatility in managing cholesterol-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ezetimibe for hypercholesterolemia. Morris, S., Tiller, R.[2015]

Statin therapy is the first-line treatment for lowering cholesterol in diabetes patients, significantly reducing their cardiovascular disease (CVD) risk, regardless of whether they have a history of CVD.

Patients with diabetes should aim for specific cholesterol levels: LDL cholesterol below 2.6 mmol/L (100 mg/dL) for those with CVD and below 2.6 mmol/L for those without, while also managing triglycerides and HDL cholesterol to further reduce CVD risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of lipid disorders in patients with diabetes. Colhoun, HM., Betteridge, DJ.[2020]

Statin therapy remains the primary treatment for lowering LDL cholesterol and preventing atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes, supported by nearly 30 years of clinical use.

Ezetimibe, PCSK9 inhibitors (alirocumab and evolocumab), and high-dose icosapent ethyl are effective add-on therapies for further reducing ASCVD risk in statin-treated patients with diabetes, particularly those with elevated triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dyslipidemia Management in Adults With Diabetes. Lazarte, J., Hegele, RA.[2020]

Statin drugs effectively lower LDL-cholesterol and reduce cardiovascular risk, but can cause side effects like muscle symptoms and diabetes, which do not outweigh their benefits.

Evolocumab, a PCSK9 inhibitor, is an effective treatment for patients with familial hypercholesterolemia who do not respond adequately to statins or ezetimibe, highlighting the importance of tailored lipid therapy based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An updated review of lipid-modifying therapy. Simons, LA.[2020]

Ezetimibe effectively lowers cholesterol by inhibiting NPC1L1 transport proteins in the intestines, and it also has anti-inflammatory properties, making it a unique treatment option for hypercholesterolemia.

The drug is safe and effective for patients with various conditions, including those who have undergone cardiac, renal, and liver transplants, as well as HIV patients, and it shows no significant interactions with most other common medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ezetimibe--a new approach in hypercholesterolemia management. Suchy, D., Łabuzek, K., Stadnicki, A., et al.[2020]

In a study involving 89 patients with newly diagnosed type 1 diabetes, atorvastatin did not significantly preserve beta cell function compared to placebo over 18 months, although there was a nonsignificant slower decline in beta cell function in the atorvastatin group.

Atorvastatin treatment resulted in significant reductions in total cholesterol and C-reactive protein levels, indicating its effectiveness in lipid-lowering and anti-inflammatory effects, but metabolic control remained similar between both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Residual beta cell function in newly diagnosed type 1 diabetes after treatment with atorvastatin: the Randomized DIATOR Trial. Martin, S., Herder, C., Schloot, NC., et al.[2022]

In a study of 136 patients with extremely high-risk acute coronary syndrome (ACS), adding the PCSK9 inhibitor evolocumab to standard treatment significantly reduced LDL cholesterol levels compared to standard treatment alone, achieving an LDL-C compliance rate of 82.35% versus 22.06%.

The use of evolocumab also led to a lower incidence of major adverse cardiovascular events (MACEs) during a 3-month follow-up (8.82% in the evolocumab group vs. 24.59% in the control group), without increasing the risk of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the Early Application of Evolocumab on Blood Lipid Profile and Cardiovascular Prognosis in Patients with Extremely High-Risk Acute Coronary Syndrome. Hao, Y., Yang, YL., Wang, YC., et al.[2022]

In a study comparing the effects of simvastatin and ezetimibe on cholesterol levels, simvastatin was significantly more effective in lowering total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes (T2DM) than in those with type 1 diabetes (T1DM).

Ezetimibe, a cholesterol absorption inhibitor, was found to be more effective than simvastatin in lowering LDL-C levels in T1DM patients, suggesting that cholesterol absorption inhibitors may be a better treatment option for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of simvastatin and ezetimibe in lowering low-density lipoprotein cholesterol in subjects with type 1 and type 2 diabetes mellitus. Ciriacks, K., Coly, G., Krishnaswami, S., et al.[2015]

In a study of 125,330 patients with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH), only 1.05% added or switched to ezetimibe therapy, highlighting its limited uptake in real-world settings.

Among those who switched to ezetimibe, only 26% achieved the LDL-C goal of < 70 mg/dL within 90 days, indicating that while ezetimibe can help lower cholesterol, its effectiveness may be limited, especially in patients with higher baseline LDL-C levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ezetimibe Use and LDL-C Goal Achievement: A Retrospective Database Analysis of Patients with Clinical Atherosclerotic Cardiovascular Disease or Probable Heterozygous Familial Hypercholesterolemia. Menzin, J., Aggarwal, J., Boatman, B., et al.[2023]

In a study of 31 patients with type 2 diabetes, high-dose simvastatin (80 mg) significantly reduced the activation of the proinflammatory transcription factor NF-κB and lowered inflammatory markers like hsCRP, indicating its strong anti-inflammatory effects.

In contrast, a combination of low-dose simvastatin (10 mg) and ezetimibe (10 mg) achieved similar LDL-cholesterol reduction but did not show any significant impact on NF-κB activation or inflammatory markers, suggesting that not all cholesterol-lowering therapies have the same anti-inflammatory benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identical LDL-cholesterol lowering but non-identical effects on NF-κB activity: High dose simvastatin vs combination therapy with ezetimibe. Rudofsky, G., Reismann, P., Groener, JB., et al.[2022]

Lipid-lowering therapy is important for reducing cardiovascular risk in individuals with type 1 diabetes (T1D), but many patients are not adequately treated for dyslipidaemia.

Surveys revealed key barriers to effective lipid management in T1D, such as a lack of awareness about cardiovascular risks, a focus on blood sugar control over cholesterol management, and concerns about statin side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient perceptions of cardiovascular risk, lipid management and statins in type 1 diabetes. Lan, NSR., Hong, RSY., Ryan, C., et al.[2023]

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Statins and Diabetes: What You Should Know

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