Acute Microvascular Changes With LDL Apheresis

Hyperlipidemia Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02388633
• Other study ID #: LDL Apheresis
• Status: Completed
• Start date: March 1, 2015
• Est. completion date: July 1, 2018

Study information

• Verified date: March 2021
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: July 1, 2018
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperlipidemia
• Hyperlipidemias

Intervention

Procedure:
• Plasmapharesis
Clinically-indicated LDL apheresis

Locations

Country	Name	City	State
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Oregon Health and Science University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Car — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial Perfusion at Rest	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	10 min
Primary	Skeletal Muscle Perfusion at During Exercise	Contrast ultrasound assessment of microvascular perfusion of forearm skeletal muscle during contractile exercise.	10 min