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Atherosclerotic Vascular DiseasePhase 4NCT03829046

The Effects of Evolocumab in Patients With Diabetes and Atherosclerotic Vascular Disease

A Phase 4 study testing Evolocumab in people with Atherosclerotic Vascular Disease and Type2 Diabetes, run by Robert Rosenson at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Experimental models have linked lipid lowering therapies with systemic inflammation; however, relatively little is known about this network in clinical populations and specifically how it changes with PCSK9 inhibition. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Evolocumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
41 participants
Where
2 sitesin 2 countries
Study dates
3 Jun 2019to 15 Nov 2021
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects ≥18 years of age signing of informed consent;
  • A history of clinical ASCVD, which is defined as: acute coronary syndrome, or a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral arterial disease presumed to be of atherosclerotic origin;
  • Clinical diagnosis of type 2 diabetes according to ADA/ CDA guidelines;
  • Subject on stable dose of maximally-tolerated statin therapy for ≥4 weeks prior to screening and LDL-c ≥70mg/dL. For subjects whose maximally tolerated dose of statin is no type or dose (i.e. determined to be statin intolerant by primary investigator), background lipid-lowering therapy is not required;
  • Fasting triglycerides ≤400mg/dL (4.52mmol/L) by central laboratory at screening;
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures;
  • Abnormal urinary Albumin Creatinine Ratio (ACR) as defined by an ACR ≥2;
  • Subject tolerates screening placebo injection.

Who cannot join

  • Personal or family history of hereditary muscular disorders;
  • NYHA III or IV heart failure, or last know left ventricular ejection fraction (LVEF) <30%;
  • Uncontrolled serious cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 6 weeks prior to randomization;
  • Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery graft (CABG) or stroke within 3 months prior to randomization;
  • Planned cardiac surgery or revascularization;
  • Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <30mL/min/1.73m2 at screening;
Show all 27Show fewer
  • Type 1 diabetes, poorly controlled type 2 diabetes (HbA1c >10%), newly diagnosed type 2 diabetes (within 6 months of randomization), or laboratory evidence of diabetes during screening (fasting serum glucose ≥126mg/dL [7.0mmol/L] or HbA1c ≥6.5% without prior diagnosis of diabetes;
  • Uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) >160mmHg or diastolic BP (DBP) >100mmHg;
  • Subject who has taken a cholesterol easter transfer protein (CETP) inhibitor in the last 12 months prior to LDL-c screening, such as: anacetrapib, dalcetrapib or evacetrapib;
  • Treatment in the last 3 months prior to LDL-c screening with any of the following drugs: systemic cyclosporine, systemic steroids (e.g. IV, intramuscular [IM], or PO) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (e.g. Accutane); (Note: vitamin A in a multivitamin preparation is permitted). Topical retinol prescription and non-prescription derivatives or creams are permitted;
  • Uncontrolled hypothyroidism or hyperthyroidism as defined by thyroid stimulating hormone (TSH) <1.0 time the lower limit of normal or >1.5 times the ULN, respectively, at screening. Potential subjects with TSH <1.0 time the lower limit of normal due to thyroid replacement therapy is not considered an exclusion;
  • Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times the ULN as determined by central laboratory analysis at screening;
  • Known active infection or major hematologic, renal metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator;
  • Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months prior to randomization;
  • Unreliability as a study participant based on the investigator's (or designee's) knowledge of the subject (e.g. alcohol or other drug abuse);
  • Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s);
  • Female subject who has either (1) not used at least 1 highly effective method of contraception for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, unless the subject is sterilized or postmenopausal;
  • Subject who is pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 15 weeks after the end of treatment;
  • Use of PCSK9 inhibitor within 10 weeks from screening;
  • Subject who has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures;
  • Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years;
  • Subject who has known sensitivity to any of the products or components to be administered during dosing;
  • Subject who is likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge;
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the principal investigator would pose a risk to subject or interfere with the study evaluation, procedures or completion;
  • Blood donation 4 weeks prior to screening, or stated intention to donate blood or blood products during the period of the study or within one month following completion of the study;
  • Subjects who have participated in other studies within 30 days prior to screening, or have five times the plasma half-life (if known) of the investigational drug, whichever is longer;
  • BMI>40kg/m2.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site
  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

Canada1 site
  • St. Michael's - University of Toronto

    Toronto, Ontario, M5B1W8

Other trials in Canada

About this study

Official title: The Effects of Evolocumab on Endothelial and Inflammatory Biocellular Markers in Patients With Diabetes and Atherosclerotic Vascular Disease (METCHNIKOFF)

Experimental models have linked lipid lowering therapies with systemic inflammation; however, relatively little is known about this network in clinical populations and specifically how it changes with PCSK9 inhibition. The eligible subjects will have 6 visits in 13 to 16 weeks and will have Repatha/placebo 140mg subcutaneous every 4 weeks for 3 times since randomization visit, blood tests will be done in each visit to evaluate the effects of evolocumab upon biocellular markers potentially altered by PCSK9 inhibition in a population of type 2 diabetes patients with microvascular dysfunction.

Primary Aims:

Read more

Determine the ACUTE and SHORT-TERM effects of PCSK9 inhibition with evolocumab on biocellular markers of inflammation, immune mediated thrombosis and rheology. The data from this trial will be used to support a clinical trial to assess the role of PCSK9 inhibition in type 2 diabetes patients with cardiac microvascular dysfunction.

Secondary Aims:

  1. To define the association between PCSK 9 concentrations and immune-related phenotype.
  2. To define the association between Lp(a) concentrations, oxidized phospholipids (OxPL), ApoB, biocellular markers of inflammation, tissue factor and immunothrombosis.
Read the detailed description

Multi-center, double-blind, randomized, placebo-controlled, parallel group Phase IV study with two treatment arms: evolocumab SC 420 mg/dL QM or matching placebo. The population will include 40 participants with documented Atherosclerotic Vascular Disease (CAD, Stroke, PAD) and type 2 diabetes who receive treatment with maximal tolerated statin therapy and stable doses of anti-hyperglycemic therapy.

Subjects will be followed for 12 weeks during the treatment phase, maintaining the double-blind throughout. Assessments of ACUTE and SHORT-TERM effects of PCSK9 inhibition with evolocumab on biocellular markers of endothelial function will be measured at baseline, Week 2, and Week 12. Safety assessments will be undertaken at each study visit.

Being tested
Placebo, Evolocumab
Keywords
PCSK9 inhibition, Evolocumab, Inflammatory Signals, Circulating monocyte subsets
Medical subject headings
Atherosclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    12 weeks of treatment

  • EvolocumabDrug

    12 weeks of treatment

Study groups in NCT03829046
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo SC QM
Receives: Drug: Placebo
EvolocumabActive comparatorEvolocumab SC 420mg/dL QM
Receives: Drug: Evolocumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Adverse Events

    Safety as measured by number of adverse events, defined as any untoward medical occurrence in a subject who has been administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

    Measured: up to 12 weeks

Secondary outcomes (10)
  1. Seattle Angina Questionnaire

    The Seattle Angina Questionnaire is a quality-of-life measure for patients with coronary artery disease. The SAQ is a self-report instrument with 19 items that yields five subscale scores: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. There is no summary score generated.

    Measured: 12 weeks

  2. MDA Level

    Malondialdehyde levels to measure oxidative stress

    Measured: 12 weeks

  3. MPO Level

    Myeloperoxidase level to measure inflammation

    Measured: 12 weeks

  4. IL-6 Level

    Interleukin-6 levels to measure cytokines

    Measured: 12 weeks

  5. IL-18 Level

    Interleukin-8 levels to measure cytokines

    Measured: 12 weeks

  6. TNF-α Level

    Tumor necrosis factor alpha levels to measure cytokines

    Measured: 12 weeks

  7. PECAM Level

    Platelet endothelial cell adhesion molecule levels to measure vascular endothelial activation

    Measured: 12 weeks

  8. ICAM Level

    Intercellular adhesion molecule levels to measure vascular endothelial activation

    Measured: 12 weeks

  9. VCAM Level

    Vascular cell adhesion molecule levels to measure vascular endothelial activation

    Measured: 12 weeks

  10. Alpha5/Beta3 Activation Levels

    Alpha 5/Beta 3 levels to measure vascular endothelial activation

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2019
  2. Study start3 Jun 2019
  3. Primary completion15 Nov 2021
  4. Study completion15 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Model description
A multi-center, double-blind, randomized, placebo-controlled, parallel group Phase IV study with two treatment arms: evolocumab SC 420 mg/dL QM or matching placebo. The identity of the treatments will be concealed by the use of matching placebo to the study drug that are identical in packaging, labeling, appearance and schedule of administration.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03829046
Sponsor's protocol ID
GCO 18-1412
Other IDs
20167719
Status last verified
Apr 2026
First submitted
1 Feb 2019
Last updated
28 Apr 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: This is a pilot study and all data from this trial will be used to support a bigger clinical trial to assess the role of PCSK9 inhibition in type 2 diabetes patients with cardiac microvascular dysfunction.

Publications

  • Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015 Feb;15(2):104-16. doi: 10.1038/nri3793.

    PubMed 25614320
  • Chatzizisis YS, Coskun AU, Jonas M, Edelman ER, Feldman CL, Stone PH. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J Am Coll Cardiol. 2007 Jun 26;49(25):2379-93. doi: 10.1016/j.jacc.2007.02.059. Epub 2007 Jun 8.

    PubMed 17599600
  • Dai G, Kaazempur-Mofrad MR, Natarajan S, Zhang Y, Vaughn S, Blackman BR, Kamm RD, Garcia-Cardena G, Gimbrone MA Jr. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14871-6. doi: 10.1073/pnas.0406073101. Epub 2004 Oct 4.

    PubMed 15466704
  • Traub O, Berk BC. Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol. 1998 May;18(5):677-85. doi: 10.1161/01.atv.18.5.677.

    PubMed 9598824
  • Nahrendorf M, Pittet MJ, Swirski FK. Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. Circulation. 2010 Jun 8;121(22):2437-45. doi: 10.1161/CIRCULATIONAHA.109.916346. No abstract available.

    PubMed 20530020
  • Chang HN, Leroueil PR, Selwa K, Gasper CJ, Tsuchida RE, Wang JJ, McHugh WM, Cornell TT, Baker JR Jr, Goonewardena SN. Profiling inflammatory responses with microfluidic immunoblotting. PLoS One. 2013 Nov 27;8(11):e81889. doi: 10.1371/journal.pone.0081889. eCollection 2013.

    PubMed 24312374
  • Rosenson RS, Tate A, Mar P, Grushko O, Chen Q, Goonewardena SN. Inhibition of PCSK9 with evolocumab modulates lipoproteins and monocyte activation in high-risk ASCVD subjects. Atherosclerosis. 2024 May;392:117529. doi: 10.1016/j.atherosclerosis.2024.117529. Epub 2024 Mar 25.

    PubMed 38583289

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Evolocumab in people with Atherosclerotic Vascular Disease and Type2 Diabetes, run by Robert Rosenson at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Adverse Events (time frame: up to 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03829046, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.

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