Impact of Triglyceride-Lowering on Inflammatory Activity in Patients with Hypertriglyceridemia

Impact of Triglyceride-Lowering on Inflammatory Activity in Patients with Hypertriglyceridemia - CIRCE

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON51943

Enrollment

Registered

2022-03-28

Start date

2022-09-20

Completion date

Unknown

Last updated

2024-04-15

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

Conditions

high levels of triglyceride Hypertriglyceridemia

Interventions

The intervention group receives 80mg AKCEA-APOCIII-LRx twice subcutaneously with an interval of four weeks, as compared to a placebo group.

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: - Adults between 18 and 75 years old - Triglycerides > 4mmol/l (350 mg/dl)

Exclusion criteria

Exclusion criteria: - Molecularly diagnosed familial chylomicronemia syndrome (homozygous and/or compound heterozygous) - Use of fibrates or fish oil: both have to be discontinued (if possible, triglyceride levels should not exceed 10 mmol/l) for at least 4 weeks prior to baseline visit - Uncontrolled diabetes (HBa1C > 90 mmol/L) - Body mass index (BMI) > 45.0 kg/m2 - Uncontrolled hypertension (systolic > 180mmHg; diastolic > 105mmHg)

Design outcomes

Primary

Measure	Time frame
The primary outcomes are: • The impact of ISIS 678354 on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16. • Postprandial triglyceride AUC change at the primary analysis time point from baseline of the treatment group as compared to placebo.	—

Secondary

Measure	Time frame
The secondary outcome is: • The mean percentage change in fasting apoC-III and triglyceride levels between the treatment and placebo group, at the primary analysis time point, compared to baseline. Exploratory study parameters/endpoints • The mean percentage change of the following parameters between the treatment and placebo group, at the primary analysis time point, compared to baseline: o Lipid parameters: LDL-C, HDL-C, VLDL-C, TC, (non-HDL-C), apoA-I, apoB, apoB48, Lp(a), remnant cholesterol (RC) (by a deika-senken assay) o Inflammatory parameters: hsCRP, IL-6, Il-1beta, IL-10, IL-18, E-selectin, P-selectin, soluble ICAM, soluble VCAM, von Willebrand factor • CD14-bead isolation of monocytes for: o Lipid droplets, lipid size with Nile Red Quantifier (NRQ) • Kinetic monocyte transendothelial migration (TEM) assay in the fasting and postprandial phase, comparing the treatment with the placebo group • Extracellular vesicle count and composition • T-cell functionality assays, in vitro cytokine production and epigenetic changes	—

Measure

Time frame

The secondary outcome is: • The mean percentage change in fasting apoC-III and triglyceride levels between the treatment and placebo group, at the primary analysis time point, compared to baseline. Exploratory study parameters/endpoints • The mean percentage change of the following parameters between the treatment and placebo group, at the primary analysis time point, compared to baseline: o Lipid parameters: LDL-C, HDL-C, VLDL-C, TC, (non-HDL-C), apoA-I, apoB, apoB48, Lp(a), remnant cholesterol (RC) (by a deika-senken assay) o Inflammatory parameters: hsCRP, IL-6, Il-1beta, IL-10, IL-18, E-selectin, P-selectin, soluble ICAM, soluble VCAM, von Willebrand factor • CD14-bead isolation of monocytes for: o Lipid droplets, lipid size with Nile Red Quantifier (NRQ) • Kinetic monocyte transendothelial migration (TEM) assay in the fasting and postprandial phase, comparing the treatment with the placebo group • Extracellular vesicle count and composition • T-cell functionality assays, in vitro cytokine production and epigenetic changes

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)