NCT02388633

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
8

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Mar 2015

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2015

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

March 4, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

March 17, 2015

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2018

Completed
2.8 years until next milestone

Results Posted

Study results publicly available

April 1, 2021

Completed
Last Updated

April 1, 2021

Status Verified

March 1, 2021

Enrollment Period

3.3 years

First QC Date

March 4, 2015

Results QC Date

June 5, 2019

Last Update Submit

March 5, 2021

Conditions

Hyperlipidemia

Outcome Measures

Primary Outcomes (2)

  • 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

  • Skeletal Muscle Perfusion at During Exercise

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

    10 min

Study Arms (1)

Plasmapharesis

Patients undergoing apheresis for elevated LDL. Patients will undergo contrast ultrasound perfusion imaging at rest and during forearm exercise at before and immediately after apheresis.

Procedure: Plasmapharesis

Interventions

PlasmapharesisPROCEDURE

Clinically-indicated LDL apheresis

Plasmapharesis

Eligibility Criteria

Age19 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Patients with hyperlipidemia undergoing clinically indicated LDL apheresis

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related 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 Cardiovasc Imaging. 2019 Aug;12(8 Pt 1):1430-1440. doi: 10.1016/j.jcmg.2018.05.001. Epub 2018 Jun 19.

    PMID: 29909101RESULT

MeSH Terms

Conditions

Hyperlipidemias

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Results Point of Contact

Title
Jonathan Lindner, MD
Organization
OregonHSU
lindnerj@ohsu.edu
5034949191

Study Officials

  • Jonathan Lindner, MD

    OSHU

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

March 4, 2015

First Posted

March 17, 2015

Study Start

March 1, 2015

Primary Completion

July 1, 2018

Study Completion

July 1, 2018

Last Updated

April 1, 2021

Results First Posted

April 1, 2021

Record last verified: 2021-03

Locations

US(1)