HyperlipidemiaNCT02388633
Acute Microvascular Changes With LDL Apheresis
An observational study of Hyperlipidemia, run by Oregon Health and Science University at 1 site in United States.
Trial summary
Severe hypercholesterolemia produced by conditions such as heterozygous familial hypercholesterolemia is associated with multiple complications including premature atherosclerotic disease. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Hyperlipidemia
- What is being tested?
- Plasmapharesis
- Type of treatment
- Surgery or procedure
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2015to 1 Jul 2018
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with hyperlipidemia undergoing clinically indicated LDL apheresis
Who may be able to join
- hypercholesterolemia (LDL >200 mg/dL)
- clinically-indicated aphersis for hyperlipidemia
- age >18 y.o.
Who cannot join
- pregnant or lactating females
- hypersensitivity to ultrasound contrast agents
- evidence for right to left or bidirectional shunt
- on anticoagulants
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
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.
Read the 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.
- Conditions
- Hyperlipidemia
- Being tested
- Plasmapharesis
- Medical subject headings
- Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlasmapharesisProcedure or surgery
Clinically-indicated LDL apheresis
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Plasmapharesis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 10 min
Skeletal Muscle Perfusion at During Exercise
Contrast ultrasound assessment of microvascular perfusion of forearm skeletal muscle during contractile exercise.
Measured: 10 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2015 (estimated)
- Study start1 Mar 2015
- Primary completion1 Jul 2018
- Study completion1 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperlipidemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonathan R. Lindner, MD, Oregon Health and Science University
- Investigators
- Jonathan Lindner, MD, Principal investigator, OSHU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02388633
- Sponsor's protocol ID
- LDL Apheresis
- Status last verified
- Mar 2021
- First submitted
- 4 Mar 2015
- Last updated
- 1 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 29909101
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Microvascular Changes With LDL Apheresis
- ClinicalTrials.gov ID
- NCT02388633
- Acronym / sponsor ID
- LDL Apheresis
- Conditions
- Hyperlipidemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- 1 Mar 2015 (actual)
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 1 Jul 2018 (actual)
- First posted
- 17 Mar 2015 (estimated)
- Results
- Posted 1 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Plasmapharesis | – | Procedure: PlasmapharesisPatients undergoing apheresis for elevated LDL. Patients will undergo contrast ultrasound perfusion imaging at rest and during forearm exercise at before and immediately after apheresis. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with hyperlipidemia undergoing clinically indicated LDL apheresis
Key inclusion criteria (3 listed)
- hypercholesterolemia (LDL >200 mg/dL)
- clinically-indicated aphersis for hyperlipidemia
- age >18 y.o.
Key exclusion criteria (4 listed)
- pregnant or lactating females
- hypersensitivity to ultrasound contrast agents
- evidence for right to left or bidirectional shunt
- on anticoagulants
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlasmapharesisClinically-indicated LDL apheresis | Procedure or surgery | Plasmapharesis |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29909101Wu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Lindner, MD principal investigator
OSHU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hyperlipidemia, run by Oregon Health and Science University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Myocardial Perfusion at Rest (time frame: 10 min). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02388633, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.