NLRP3 and SASP in Vazkepa therapy in patients with heart disease with or without type 2 diabetes

Does Vazkepa mitigate the negative effects of metabolic memory in monocyte-derived macrophages isolated from patients with cardiovascular disease +/- type 2 diabetes?

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

ISRCTN

Registry ID

ISRCTN64669648

Enrollment

Registered

2025-03-31

Start date

2024-04-26

Completion date

Unknown

Last updated

2026-05-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Atherosclerotic cardiovascular disease with or without type 2 diabetes mellitus Circulatory System

Interventions

This is a single-centre prospective open-labelled observational cohort study with randomisation, involving human blood samples and data collection from patients randomised to one of two groups to ensu

Eligibility

Sex/Gender

All

Age

18 Years to 85 Years

Inclusion criteria

Inclusion criteria: 1. Patients with established ASCVD 2. Previous event of acute myocardial infarction (AMI) 3. Previous percutaneous coronary intervention (PCI) 4. With or without known T2DM 5. If diabetic, is established and stable on diabetes oral medication 6. Established and stable on statin and/or ezetimibe therapy 7. Low-density lipoprotein cholesterol (LDL-C) levels above 1.04 mmol/litre and below or equal to 2.60 mmol/litre 8. Raised fasting triglycerides (1.7 mmol/litre or above) 9. Eligible for Vazkepa therapy within licenced indication and NICE guideline criteria 10. Able to provide informed consent

Exclusion criteria

Exclusion criteria: 1. Contraindications to Vazkepa therapy 2. Concurrent or planned bempedoic acid or inclisiran or PCSK9 therapy 3. Pregnancy or breastfeeding 4. Severe end-stage kidney failure 5. Severe end-stage liver disease 6. Other conditions that would reduce the expected life span of a patient to less than 2 years 7. Unable to provide informed consent 8. Acute renal failure 9. Cardiogenic shock 10. Severe valvular heart disease 11. Recent acute cardiac event, revascularisation, or surgery (within 3 months) 12. Recent infective event (within 3 months) 13. Active inflammatory-related conditions, including infection, cancer, or autoimmune disease

Design outcomes

Primary

Measure	Time frame
Measured in blood samples taken from patients with Vazkepa-IPE prescribed (Arm A, 34 patients, blood sampled at day 0, 30, 90 and 180), (Arm B, 34 patients blood sampled at day 120, 180) vs without Vazkepa (Arm B (control), 34 patients, blood sampled at day 0, 30 and 90). To elucidate the role of Vazkepa-IPE in regulating (reducing) specific inflammatory responses in patients with established ASCVD, the researchers shall determine the ability of Vazkepa (vs no Vazkepa) to: 1. Blunt the priming/activation of specific inflammatory responses (the NLRP3 inflammasome complex) in activated monocyte-derived macrophages isolated from peripheral blood mononuclear cells. Measured using quantitative real-time PCR and a caspase assay at time=0, 30,90,180 (Arm A) (n = 34) and time=120,180 (Arm B) compared to no Vazkepa time=0, 30, 90 (Arm B) (n = 34). 2. Determine whether this leads to a decrease in accelerated cell aging and sustained tissue damage by measuring a decrease in senescent cell accumulation and a decrease in the accumulation of the senescence-associated secretory phenotype (SASP). Measured using quantitative real-time PCR and plasma/serum biomarkers at time=0, 30,90,180 (Arm A)(n=34) and time=120,180 (Arm B) compared to no Vazkepa time=0, 30, 90 (Arm B) (n=34). 3. Examine cell-cell communication by measuring if Vazkepa suppresses connexin-43 hemichannel mediated ATP release in activated monocyte-derived-macrophages. Measured through ATP release at time=0, 30,90,180 (Arm A) (n = 34) and time=120,180 (Arm B) compared to no Vazkepa time=0, 30, 90 (Arm B) (n = 34).	—

Measure

Time frame

Measured in blood samples taken from patients with Vazkepa-IPE prescribed (Arm A, 34 patients, blood sampled at day 0, 30, 90 and 180), (Arm B, 34 patients blood sampled at day 120, 180) vs without Vazkepa (Arm B (control), 34 patients, blood sampled at day 0, 30 and 90). To elucidate the role of Vazkepa-IPE in regulating (reducing) specific inflammatory responses in patients with established ASCVD, the researchers shall determine the ability of Vazkepa (vs no Vazkepa) to: 1. Blunt the priming/activation of specific inflammatory responses (the NLRP3 inflammasome complex) in activated monocyte-derived macrophages isolated from peripheral blood mononuclear cells. Measured using quantitative real-time PCR and a caspase assay at time=0, 30,90,180 (Arm A) (n = 34) and time=120,180 (Arm B) compared to no Vazkepa time=0, 30, 90 (Arm B) (n = 34). 2. Determine whether this leads to a decrease in accelerated cell aging and sustained tissue damage by measuring a decrease in senescent cell accumulation and a decrease in the accumulation of the senescence-associated secretory phenotype (SASP). Measured using quantitative real-time PCR and plasma/serum biomarkers at time=0, 30,90,180 (Arm A)(n=34) and time=120,180 (Arm B) compared to no Vazkepa time=0, 30, 90 (Arm B) (n=34). 3. Examine cell-cell communication by measuring if Vazkepa suppresses connexin-43 hemichannel mediated ATP release in activated monocyte-derived-macrophages. Measured through ATP release at time=0, 30,90,180 (Arm A) (n = 34) and time=120,180 (Arm B) compared to no Vazkepa time=0, 30, 90 (Arm B) (n = 34).

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Secondary

Measure	Time frame
1. The difference in baseline activity in the chronic stable disease phase of ASCVD (before Vazkepa-IPE therapy) of the Primary Outcome Measures above: of NLRP3 (Measure1), SASP (Measure2) and Cx43 (Measure3) to T2DM status (with T2DM vs without), by measuring caspase-1, ATP release and mRNA expression in PBMC-derived macrophages isolated and differentiated from blood samples taken from patients before starting their Vazkepa-IPE medication (T2DM patients in Arm A Day 0 and in Arm B Day 0, 30 and 90 [n = 34], vs non-diabetics in Arm A Time = 0 and in Arm B Time = 0, 30 and 90 [n=34]). 2. Correlate the magnitude of effect with Vazkepa-IPE therapy of the Primary Outcome Measures above: of NLRP3 (Measure1), SASP (Measure2) and Cx43 (Measure3) to T2DM status (with T2DM vs without), by measuring caspase-1, ATP release and mRNA expression in PBMC-derived macrophages isolated and differentiated from samples taken from patients starting their Vazkepa-IPE medication during the initial 3 months (T2DM patients in Arm A Time = 0, 30 and 90 and in Arm B Time=90, 120 and 180 [n = 34], vs non-diabetics in Arm A Time=0, 30 and 90 and in Arm B Time=90, 120 and 180 [n = 34]). 3. The variation/difference in the baseline activity of NLRP3 (Measure 1), SASP (Measure 2) and Cx43 (Measure 3) in patients without Vazkepa therapy, by measuring caspase-1, ATP release and mRNA expression in the series of pair-wise blood samples taken over 3 months from patients without Vazkepa therapy (Arm B Time = 0, 30 and 90, n = 34) 4. Determine whether the effect of Vazkepa on NLRP3 (Measure 1), SASP (Measure 2) and Cx43 (Measure 3) correlates and extends to day 180 of Vazkepa therapy by measuring caspase-1, ATP release and mRNA expression (Arm A Time = 0, 30, 90 and 180, n = 34).	—

Measure

Time frame

1. The difference in baseline activity in the chronic stable disease phase of ASCVD (before Vazkepa-IPE therapy) of the Primary Outcome Measures above: of NLRP3 (Measure1), SASP (Measure2) and Cx43 (Measure3) to T2DM status (with T2DM vs without), by measuring caspase-1, ATP release and mRNA expression in PBMC-derived macrophages isolated and differentiated from blood samples taken from patients before starting their Vazkepa-IPE medication (T2DM patients in Arm A Day 0 and in Arm B Day 0, 30 and 90 [n = 34], vs non-diabetics in Arm A Time = 0 and in Arm B Time = 0, 30 and 90 [n=34]). 2. Correlate the magnitude of effect with Vazkepa-IPE therapy of the Primary Outcome Measures above: of NLRP3 (Measure1), SASP (Measure2) and Cx43 (Measure3) to T2DM status (with T2DM vs without), by measuring caspase-1, ATP release and mRNA expression in PBMC-derived macrophages isolated and differentiated from samples taken from patients starting their Vazkepa-IPE medication during the initial 3 months (T2DM patients in Arm A Time = 0, 30 and 90 and in Arm B Time=90, 120 and 180 [n = 34], vs non-diabetics in Arm A Time=0, 30 and 90 and in Arm B Time=90, 120 and 180 [n = 34]). 3. The variation/difference in the baseline activity of NLRP3 (Measure 1), SASP (Measure 2) and Cx43 (Measure 3) in patients without Vazkepa therapy, by measuring caspase-1, ATP release and mRNA expression in the series of pair-wise blood samples taken over 3 months from patients without Vazkepa therapy (Arm B Time = 0, 30 and 90, n = 34) 4. Determine whether the effect of Vazkepa on NLRP3 (Measure 1), SASP (Measure 2) and Cx43 (Measure 3) correlates and extends to day 180 of Vazkepa therapy by measuring caspase-1, ATP release and mRNA expression (Arm A Time = 0, 30, 90 and 180, n = 34).

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Countries

England, United Kingdom

Contacts

Public ContactKelvin Lee

kelvin.lee@nhs.net+44 (0)1522 512512

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: May 7, 2026