Ignite Creation Date:
2025-12-25 @ 3:02 AM
Ignite Modification Date:
2026-07-11 @ 9:31 AM
Study NCT ID:
NCT02388633
Status:
COMPLETED
Last Update Posted:
2021-04-01
First Post:
2015-03-04
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Acute Microvascular Changes With LDL Apheresis
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006949', 'term': 'Hyperlipidemias'}], 'ancestors': [{'id': 'D050171', 'term': 'Dyslipidemias'}, {'id': 'D052439', 'term': 'Lipid Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'lindnerj@ohsu.edu', 'phone': '5034949191', 'title': 'Jonathan Lindner, MD', 'organization': 'OregonHSU'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': '1 week', 'eventGroups': [{'id': 'EG000', 'title': 'Plasmapharesis', 'description': '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.\n\nPlasmapharesis: Clinically-indicated LDL apheresis', 'otherNumAtRisk': 8, 'deathsNumAtRisk': 8, 'otherNumAffected': 0, 'seriousNumAtRisk': 8, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Myocardial Perfusion at Rest', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Plasmapharesis', 'description': '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.\n\nPlasmapharesis: Clinically-indicated LDL apheresis'}], 'classes': [{'title': 'Pre-apheresis', 'categories': [{'measurements': [{'value': '55', 'spread': '21', 'groupId': 'OG000'}]}]}, {'title': 'Post apheresis', 'categories': [{'measurements': [{'value': '135', 'spread': '65', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '10 min', 'description': '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', 'unitOfMeasure': 'IU/s', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Skeletal Muscle Perfusion at During Exercise', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Plasmapharesis', 'description': '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.\n\nPlasmapharesis: Clinically-indicated LDL apheresis'}], 'classes': [{'title': 'Pre-apheresis', 'categories': [{'measurements': [{'value': '116', 'groupId': 'OG000', 'lowerLimit': '76', 'upperLimit': '188'}]}]}, {'title': 'Post apheresis', 'categories': [{'measurements': [{'value': '118', 'groupId': 'OG000', 'lowerLimit': '52', 'upperLimit': '249'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '10 min', 'description': 'Contrast ultrasound assessment of microvascular perfusion of forearm skeletal muscle during contractile exercise.', 'unitOfMeasure': 'IU/s', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Plasmapharesis', 'description': '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.\n\nPlasmapharesis: Clinically-indicated LDL apheresis'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Plasmapharesis', 'description': '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.\n\nPlasmapharesis: Clinically-indicated LDL apheresis'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '56', 'spread': '11', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-06-05', 'size': 183074, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2020-06-02T15:17', 'hasProtocol': True}, {'date': '2019-06-05', 'size': 268273, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2020-06-02T15:17', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 8}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-03-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-03', 'completionDateStruct': {'date': '2018-07-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-03-05', 'studyFirstSubmitDate': '2015-03-04', 'resultsFirstSubmitDate': '2019-06-05', 'studyFirstSubmitQcDate': '2015-03-13', 'lastUpdatePostDateStruct': {'date': '2021-04-01', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-03-05', 'studyFirstPostDateStruct': {'date': '2015-03-17', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-04-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-07-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Myocardial Perfusion at Rest', 'timeFrame': '10 min', 'description': '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'}, {'measure': 'Skeletal Muscle Perfusion at During Exercise', 'timeFrame': '10 min', 'description': 'Contrast ultrasound assessment of microvascular perfusion of forearm skeletal muscle during contractile exercise.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Hyperlipidemia']}, 'referencesModule': {'references': [{'pmid': '29909101', 'type': 'RESULT', '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '19 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Patients with hyperlipidemia undergoing clinically indicated LDL apheresis', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* hypercholesterolemia (LDL \\>200 mg/dL)\n* clinically-indicated aphersis for hyperlipidemia\n* age \\>18 y.o.\n\nExclusion Criteria:\n\n* pregnant or lactating females\n* hypersensitivity to ultrasound contrast agents\n* evidence for right to left or bidirectional shunt\n* on anticoagulants'}, 'identificationModule': {'nctId': 'NCT02388633', 'briefTitle': 'Acute Microvascular Changes With LDL Apheresis', 'organization': {'class': 'OTHER', 'fullName': 'Oregon Health and Science University'}, 'orgStudyIdInfo': {'id': 'LDL Apheresis'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Plasmapharesis', 'description': '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.', 'interventionNames': ['Procedure: Plasmapharesis']}], 'interventions': [{'name': 'Plasmapharesis', 'type': 'PROCEDURE', 'description': 'Clinically-indicated LDL apheresis', 'armGroupLabels': ['Plasmapharesis']}]}, 'contactsLocationsModule': {'locations': [{'zip': '97239', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Oregon Health & Science University', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}], 'overallOfficials': [{'name': 'Jonathan Lindner, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'OSHU'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Oregon Health and Science University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Jonathan R. Lindner, MD', 'investigatorAffiliation': 'Oregon Health and Science University'}}}}