Acute Microvascular Changes With LDL Apheresis

Severe hypercholesterolemia produced by conditions such as heterozygous familial hypercholesterolemia is associated with multiple complications including premature atherosclerotic disease. There is evidence that microvascular perfusion, particularly flow reserve, in critical organs is limited due to abnormalities in plasma viscosity, abnormal RBC deformability, and an imbalance between vasodilators and vasoconstrictors. There is little is currently known about acute changes in microvascular blood flow and microvascular rheology that occur in response to plasmapharesis which is used in some patients to lower critically elevated cholesterol levels. Our research group has pioneered CEU methods for assessing myocardial and skeletal muscle perfusion, and has previously demonstrated in pre-clinical models that acute hyperlipidemia produces a reduction in microvascular RBC transit rate. In this study, the investigators will assess acute changes in microvascular perfusion in patients undergoing clinically-indicated plasmapharesis.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hyperlipidemia Dyslipidemias Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

19 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Oregon Health & Science University

Portland, Oregon, 97239, United States

About this study

Subjects who are scheduled to have planned apheresis treatment for severe hypercholesterolemia will be recruited into the study. They will undergo a screening evaluation, including a medical history, physical examination, ECG, and limited echocardiogram to evaluate for exclusion criteria. Before the apheresis procedure, blood samples will be obtained for plasma markers of inflammation, erythrocyte deformability, and plasma viscosity. Contrast enhanced ultrasound perfusion imaging will be performed to evaluate blood flow in the myocardium at rest, as well as in the forearm skeletal muscle before and after mild isometric exercise (50% maximal grip, 0.2 Hz). Flow mediated vasodilation will be performed. The subjects will then undergo their planned apheresis procedure. Within 2 hours of completion of apheresis, blood collection and CEU will be repeated. Plasma lipids will be available as part of the standard apharesis protocol.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

hypercholesterolemia (LDL >200 mg/dL)
clinically-indicated aphersis for hyperlipidemia
age >18 y.o.

Exclusion criteria

pregnant or lactating females
hypersensitivity to ultrasound contrast agents
evidence for right to left or bidirectional shunt
on anticoagulants

Treatment and study plan

Plasmapharesis

Procedure

Clinically-indicated LDL apheresis

Primary outcomes

Myocardial Perfusion at Rest

Time frame: 10 min

Acoustic intensity data were fit to the following function: y = A(1-e^-beta*t) where y is signal intensity at time t, A is the plateau intensity reflecting relative microvascular blood volume (MBV), and beta is the rate constant reflecting microvascular blood flux rate. Microvascular blood flow was quantified by the product of MBV and beta
Skeletal Muscle Perfusion at During Exercise

Time frame: 10 min

Contrast ultrasound assessment of microvascular perfusion of forearm skeletal muscle during contractile exercise.

Sponsors and collaborators

Lead sponsor

Oregon Health and Science University

Other

Registry information

Important dates

Study start: 2015
Primary completion: 2018
Study completion: 2018
First posted: Mar 17, 2015
Registry last updated: Apr 1, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed