SIALIDASE INHIBITION AS ANTIATHEROSCLEROTIC THERAPY

NCT06590012 | Active Not Recruiting Phase 2

• 1 other identifier: Ter-07082024
• Study Type: interventional
• Target: 1,228
• Locations: 1 country
• Sites: 10

Brief Summary

The aim of this double-blind, randomized, placebo-controlled, multicenter study is to evaluate the pathogenetic effects of the dietary supplement "Tertinat" on a fundamental mechanism of atherosclerosis development: its ability to inhibit pathological desialylation of low-density lipoproteins (LDL). According to the protocol's scientific hypothesis, the loss of sialic acid from the surface of LDL converts them into highly atherogenic particles, which are actively captured by vascular macrophages, triggering the formation of unstable atherosclerotic plaques. Over 24 months of daily administration of 330 mg of epigallocatechin-3-gallate, along with standard therapy, will evaluate not only the incidence of major cardiovascular events (MACE) in atherosclerotic patients who have undergone the procedure of surgical revascularization, but also the direct dynamics of recovery of sialic acid levels in LDL particles in patients' blood. The study aims to confirm that preventing LDL desialylation reduces overall serum atherogenicity, prevents cholesterol accumulation within macrophages in vivo, and thereby provides a proven clinical effect - a reduced risk of myocardial infarction, stroke, unstable angina, heart failure, and the need for repeated revascularization in patients after coronary artery bypass grafting or stenting.

Conditions

Atherosclerosis; Atheroscleroses, Coronary; Carotid Atherosclerosis

Keywords

atherosclerosis; lipoproteins; coronary atherosclerosis; carotid atherosclerosis

Outcome Measures

Primary Outcomes (3)

• The rate of fatal cardiovascular events

  \- Cardiovascular death (death from myocardial infarction, other forms of coronary heart disease; death from stroke) The deaths from other non-coronary cardiovascular diseases and from definitively non-atherosclerotic causes of death are registered but not considered as primary endpoints.

  Evaluated in 12 and 24 months from revascularization interventions

• The rate of non-fatal cardiovascular events

  * Non-fatal myocardium infarction * Non-fatal stroke / transient ischemic attack * Unstable angina / Acute coronary syndrome * Heart failure / Hospitalization due to critical ischemia

  Evaluated in 12 and 24 months from revascularization interventions

• The rate of repeated revascularization procedures

  * Percutaneous Endovascular Interventions (PEI): Angioplasty (PTCA); Stenting; Atherectomy * Surgical Revascularization: Coronary Artery Bypass Grafting (CABG); Peripheral Artery Bypass; Endarterectomy * Medical \& Emerging Revascularization: Thrombolytic Therapy ("Clot Busters")

  Evaluated in 12 and 24 months from revascularization interventions

Secondary Outcomes (5)

• The change in the extent of stenosis of the affected coronary, carotid and femoral arteries

  Evaluated in 12 and 24 months from revascularization interventions

• The change in LDL sialic acid content

  Evaluated in 12 and 24 months from revascularization interventions

• The change in blood serum-induced intracellular cholesterol accumulation (serum atherogenicity)

  Evaluated in 12 and 24 months from revascularization interventions

• The change in total cholesterol, HDL cholesterol, triglycerides, LDL cholesterol

  Evaluated in 12 and 24 months from revascularization interventions

• The change in the cholesterol level of circulating immune complexes

  Evaluated in 12 and 24 months from revascularization interventions

Study Arms (2)

Tertinat

EXPERIMENTAL

Drug: Tertinat

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

Participants will take the placebo capsules in addition to standard treatment for 2 years.

Placebo

Tertinat DRUG

Participants will take Tertinat capsules in addition to standard treatment for 2 years.

Tertinat

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 45-75
• Atherosclerotic cardiovascular diseases may include coronary heart disease, and/or coronary atherosclerosis, and/or atherosclerosis of brachiocephalic / limb / renal arteries.
• Patients who have undergone instrumental and laboratory examinations (ECG, ultrasound / CT / angiography, biochemical tests - total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, blood glucose, C-reactive protein), and the data from above examinations from medical records are available.
• The signed informed consent.

You may not qualify if:

• Critical and urgent cardiovascular conditions: tissue ischemia stage III-IV, stroke, acute coronary syndrome, acute myocardial infarction, chronic heart failure III and IV class NYHA (New York Heart Association).
• Other critical and urgent conditions not associated with cardiovascular diseases, including the need for urgent interventions, chronic renal failure stages IV-V (creatinine clearance \< 30 ml / min according to the Cockcroft-Gault Equation)
• Systemic autoimmune diseases in medical history, including: rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroiditis, autoimmune vasculitis, ulcerative colitis.
• Significant weight loss (\> 10% of body weight in the previous year) of unknown etiology.
• Conditions that limit adherence to participation in the study (dementia, neuropsychiatric diseases, drug addiction, alcoholism, etc.).
• Participation in other clinical studies (or use of investigational substances) within 3 months prior to study entry.
• Carriers of HIV or viral hepatitis
• Pregnancy or breast feeding
• Refusal to participate in the study / to sigh informed concent.

Sponsors & Collaborators

• Institute for Atherosclerosis Research, Russia: lead

Study Sites (10)

State Autonomous Healthcare Institution "Interregional Clinical Diagnostic Center"

Kazan', 420101, Russia

Location

Research Institute for Complex Issues of Cardiovascular Diseases

Kemerovo, 650000, Russia

Location

Lipetsk Regional Clinical Hospital

Lipetsk, 398055, Russia

Location

A. V. Vishnevsky National Medical Research Center of Surgery (Federal State Budgetary Institution)

Moscow, 117997, Russia

Location

M. F. Vladimirsky Moscow Regional Research Clinical Institute

Moscow, 129110, Russia

Location

LLC "RC Medical"

Novosibirsk, 630005, Russia

Location

City Polyclinic No. 109 (State Budgetary Healthcare Institution)

Saint Petersburg, 192283, Russia

Location

Llc "Sfera-Med"

Saint Petersburg, 197342, Russia

Location

Cardiology Research Institute - Branch of the Federal State Budgetary Scientific Institution "Tomsk National Research Medical Center of the Russian Academy of Sciences"

Tomsk, 634012, Russia

Location

N. N. Burdenko Voronezh State Medical University

Voronezh, 394036, Russia

Location

Related Publications (15)

• Mezentsev A, Bezsonov E, Kashirskikh D, Baig MS, Eid AH, Orekhov A. Proatherogenic Sialidases and Desialylated Lipoproteins: 35 Years of Research and Current State from Bench to Bedside. Biomedicines. 2021 May 25;9(6):600. doi: 10.3390/biomedicines9060600.

  PMID: 34070542 BACKGROUND

• Liu Y, Zhang H, Dai X, Zhu R, Chen B, Xia B, Ye Z, Zhao D, Gao S, Orekhov AN, Zhang D, Wang L, Guo S. A comprehensive review on the phytochemistry, pharmacokinetics, and antidiabetic effect of Ginseng. Phytomedicine. 2021 Nov;92:153717. doi: 10.1016/j.phymed.2021.153717. Epub 2021 Sep 10.

  PMID: 34583224 BACKGROUND

• Simental-Mendia LE, Shah N, Sathyapalan T, Majeed M, Orekhov AN, Jamialahmadi T, Sahebkar A. Effect of Curcumin on Glycaemic and Lipid Parameters in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Reprod Sci. 2022 Nov;29(11):3124-3133. doi: 10.1007/s43032-021-00761-6. Epub 2021 Oct 15.

  PMID: 34655047 BACKGROUND

• P Karagodin V, I Summerhill V, Yet SF, Orekhov AN. The Anti-atherosclerotic Effects of Natural Polysaccharides: From Phenomena to the Main Mechanisms of Action. Curr Pharm Des. 2022;28(22):1823-1832. doi: 10.2174/1381612828666220518095025.

  PMID: 35585810 BACKGROUND

• Glanz V, Bezsonov EE, Soldatov V, Orekhov AN. Thirty-Five-Year History of Desialylated Lipoproteins Discovered by Vladimir Tertov. Biomedicines. 2022 May 19;10(5):1174. doi: 10.3390/biomedicines10051174.

  PMID: 35625910 BACKGROUND

• Markina YV, Kirichenko TV, Markin AM, Yudina IY, Starodubova AV, Sobenin IA, Orekhov AN. Atheroprotective Effects of Glycyrrhiza glabra L. Molecules. 2022 Jul 22;27(15):4697. doi: 10.3390/molecules27154697.

  PMID: 35897875 BACKGROUND

• Hassanizadeh S, Shojaei M, Bagherniya M, Orekhov AN, Sahebkar A. Effect of nano-curcumin on various diseases: A comprehensive review of clinical trials. Biofactors. 2023 May-Jun;49(3):512-533. doi: 10.1002/biof.1932. Epub 2023 Jan 6.

  PMID: 36607090 BACKGROUND

• Dabravolski SA, Sukhorukov VN, Melnichenko AA, Khotina VA, Orekhov AN. Oligosaccharides as Potential Therapeutics against Atherosclerosis. Molecules. 2023 Jul 17;28(14):5452. doi: 10.3390/molecules28145452.

  PMID: 37513323 BACKGROUND

• Dabravolski SA, Sukhorukov VN, Melnichenko AA, Khotina VA, Orekhov AN. Potential Application of the Plant-Derived Essential Oils for Atherosclerosis Treatment: Molecular Mechanisms and Therapeutic Potential. Molecules. 2023 Jul 26;28(15):5673. doi: 10.3390/molecules28155673.

  PMID: 37570643 BACKGROUND

• Poznyak AV, Kashirskikh DA, Postnov AY, Popov MA, Sukhorukov VN, Orekhov AN. Sialic acid as the potential link between lipid metabolism and inflammation in the pathogenesis of atherosclerosis. Braz J Med Biol Res. 2023 Dec 11;56:e12972. doi: 10.1590/1414-431X2023e12972. eCollection 2023.

  PMID: 38088673 BACKGROUND

• Orekhov A, Sukhorukov V, Melnichenko A. Is Oxidized Low-Density Lipoprotein a Principal Actor in Atherogenesis? Curr Med Chem. 2024;31(42):6909-6910. doi: 10.2174/0109298673283640231208103306. No abstract available.

  PMID: 38185888 BACKGROUND

• Orekhov A, Khotina V, Sukhorukov V, Sobenin I. Non-oxidative vs Oxidative Forms of Modified Low-density Lipoprotein: What is More Important in Atherogenesis? Curr Med Chem. 2024;31(17):2309-2313. doi: 10.2174/0109298673294245240102105814. No abstract available.

  PMID: 38204226 BACKGROUND

• Orekhov AN. We Must Abandon the Myth: Oxidized Low-density Lipoprotein is not a Lipoprotein that Plays a Key Role in Atherogenesis. Curr Med Chem. 2025;32(15):2899-2914. doi: 10.2174/0109298673301236240311113807.

  PMID: 38494931 BACKGROUND

• Poznyak AV, Yakovlev AA, Popov Mcapital A, Cyrillic, Zhuravlev AD, Sukhorukov VN, Orekhov AN. WITHDRAWN: Coronary atherosclerotic plaque regression strategies. J Biomed Res. 2024 May 29:1-21. doi: 10.7555/JBR.37.20230223. Online ahead of print.

  PMID: 38808553 BACKGROUND

• Kashirskikh D, Chicherina N, Glanz V, Orekhov A, Sobenin I. Mouse Model of Low-density Lipoprotein Desialylation In Vivo. Curr Med Chem. 2026;33(8):1523-1537. doi: 10.2174/0109298673294745240528092506.

  PMID: 38831578 BACKGROUND

MeSH Terms

Conditions

Atherosclerosis; Coronary Artery Disease; Carotid Artery Diseases

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Alexander N. Orekhov, Prof., PhD, DSci

  Institute for Atherosclerosis Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: A randomized, double-blinded, placebo-controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized controlled trial with two parallel groups of participants

Study Record Dates

• First Submitted: August 30, 2024
• First Posted: September 19, 2024
• Study Start: August 29, 2024
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Beginning 3 months and ending 3 years after the publication of results
• Access Criteria: Data sharing agreement must be signed and submitted via direct e-mail contacts.

Locations

RU (10)