Clinical trial NCT02388633: Acute Microvascular Changes With LDL Apheresis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hyperlipidemia
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2015-03-17
Enrollment: 8
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with hyperlipidemia undergoing clinically indicated LDL apheresis

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Myocardial Perfusion at Rest
timeFrame: 10 min
measure: Skeletal Muscle Perfusion at During Exercise
timeFrame: 10 min
Secondary outcomes:
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: OSHU
name: Jonathan Lindner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu MD, Moccetti F, Brown E, Davidson BP, Atkinson T, Belcik JT, Giraud G, Duell PB, Fazio S, Tavori H, Tsimikas S, Lindner JR. Lipoprotein Apheresis Acutely Reverses Coronary Microvascular Dysfunction in Patients With Severe Hypercholesterolemia. JACC Cardiovasc Imaging. 2019 Aug;12(8 Pt 1):1430-1440. doi: 10.1016/j.jcmg.2018.05.001. Epub 2018 Jun 19.