To study the impact of AKCEA-APOCIII-LRx on lipid and inflammatory measurements in the fasting and postprandial phase.
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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
Background summary
Hypertriglyceridemia is an independent risk factor for atherosclerotic
cardiovascular disease with no therapeutic options currently widely adopted.
AKCEA-APOCIII-LRx is a promising novel drug, targeting apolipoprotein CIII (Apo
CIII), an important regulator of triglyceride metabolism. Is has been shown to
effectively and safely reduce triglyceride levels. However, its effect on
inflammatory pathways, an important driver of atherosclerosis, remains to be
elucidated.
Study objective
To study the impact of AKCEA-APOCIII-LRx on lipid and inflammatory measurements
in the fasting and postprandial phase.
Study design
A placebo controlled randomized clinical trial with 30 participants.
Intervention
The intervention group receives 80mg AKCEA-APOCIII-LRx twice subcutaneously
with an interval of four weeks, as compared to a placebo group.
Study burden and risks
Participants will be randomized to either AKCEA-APOCIII-LRx or placebo and will
be subjected to several blood testing, both in the fasting and the postprandial
phase. AKCEA-APOCIII-LRx provides specific uptake in the lever, thereby
increasing efficacy while minimizing side-effects. With only known injection
site reactions, AKCEA-APOCIII-LRx can safely be administered, resulting in a
low risk for participants. The burden associated with participation entails
multiple blood withdrawals and two oral fatloads. The yield for participants
lies in the contribution to current knowledge of this drug. In the future,
patients will benefit from an effective treatment when there is a drug on the
market, this research will aid this purpose.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- Adults between 18 and 75 years old
- Triglycerides > 4mmol/l (350 mg/dl)
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
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-003168-28-NL |
| CCMO | NL77458.000.21 |