Carotid Plaque Characteristics by MRI in AIM-HIGH (Carotid MRI Substudy)
7 februari 2018 bijgewerkt door: Xue-Qiao Zhao, University of Washington
Carotid Plaque Characteristics by MRI in AIM-HIGH
Heart attacks and strokes caused by the unstable atherosclerotic plaques remain the leading cause of death in the United States.
Unstable plaques often have more fat than stable plaques.
This study will investigate if a treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone would more effectively reduce the plaque fat content assessed by magnetic resonance imaging (MRI), therefore, further reducing heart attacks and strokes.
Studie Overzicht
Toestand
Voltooid
Interventie / Behandeling
Gedetailleerde beschrijving
Although studies have suggested that plaque morphology and composition are important determinants of plaque stability, our understanding on plaque tissue components is mainly from histological studies until recent development in MRI technique. A low level of HDL is associated with higher risk of cardiovascular events and increased amount of lipid content in the carotid plaques. Treatment with LDL-lowering plus HDL-raising compared with LDL-lowering alone more effectively protects against atherosclerosis progression. It is widely believed that HDL or its apolipoproteins mediate the removal of excess free cholesterol from peripheral cells and the cholesterol is delivered via either LDL or HDL to the liver for excretion into the bile. However, it has not been tested and approved in human atherosclerotic condition in vivo. The NIH/Abbott-funded multi-center AIM-HIGH trial is designed to compare the clinical efficacy of LDL-lowering alone with statin versus LDL-lowering plus HDL-raising with statin plus nicotinic acid combination therapy in patients with established vascular disease and high triglycerides and low HDL.
We propose to conduct a carotid MRI sub-study in 220 subjects enrolled in AIM-HIGH to investigate the important vascular biological mechanisms of HDL-raising therapy. Image collection will occur at 3 timepoints. The hypotheses and specific aims are:
- (1) To test the primary hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the mean plaque lipid composition in carotid arteries assessed by MRI.
- (2) To test the hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the plaque burden including volume and wall thickness.
- (3) To test the hypothesis that increased plaque lipid composition or vessel wall thickness by MRI is associated with increased risk of cardiovascular events.
- (4)To test a hypothesis that LDL-lowering plus HDL-raising, compared to LDL-lowering alone, will promote more rapid plaque lipid depletion. And determine the time-course of atherosclerotic plaque lipid depletion during lipid therapy.
- (5) To examine the association of clinical risk factors, lipids, lipoprotein heterogeneity, inflammatory markers and carotid plaque characteristics.
This MRI sub-study offers a unique opportunity to investigate the effectiveness of LDL-lowering plus HDL-raising therapy on human atherosclerotic plaque in vivo, to examine the association of plaque characteristics both lipid composition and volume assessed by MRI and cardiovascular outcome, and to gain novel insights in our understanding of atherosclerotic plaque pathology and the mechanisms of intensive lipid management in preventing cardiovascular events.
Studietype
Observationeel
Inschrijving (Werkelijk)
230
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Alberta
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Calgary, Alberta, Canada, T2E-7C5
- Heart Health Institute
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Calgary, Alberta, Canada, T2N-2T9
- University Of Calgary
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British Columbia
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Vancouver, British Columbia, Canada, V5Z-1M9
- Vancouver General Hospital
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Ontario
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London, Ontario, Canada, N6A-5A5
- University of Western Ontario
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Arizona
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Phoenix, Arizona, Verenigde Staten, 85032
- Cardiovascular Consultants
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California
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Long Beach, California, Verenigde Staten, 90822
- Long Beach VA Medical Center
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Los Angeles, California, Verenigde Staten, 90033
- University of Southern California
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21201
- University of Maryland
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Baltimore, Maryland, Verenigde Staten, 21205
- Johns Hopkins University
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Minnesota
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Rochester, Minnesota, Verenigde Staten, 55905
- Mayo Clinic
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North Carolina
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Durham, North Carolina, Verenigde Staten, 27710
- Duke University
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Winston-Salem, North Carolina, Verenigde Staten, 27157
- Wake Forest University
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Pennsylvania
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Philadelphia, Pennsylvania, Verenigde Staten, 19104
- Philadelphia VA Medical Center
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Texas
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Houston, Texas, Verenigde Staten, 77030
- Baylor College of Medicine
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Houston, Texas, Verenigde Staten, 77030
- Methodist Hospital
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Houston, Texas, Verenigde Staten, 77030
- Kelsey Research Foundation
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Washington
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Seattle, Washington, Verenigde Staten, 98104
- Harborview Medical Center
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Seattle, Washington, Verenigde Staten, 98105
- University of Washington
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Seattle, Washington, Verenigde Staten, 98108
- Puget Sound VA Medical Center, Seattle Campus
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
45 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Bemonsteringsmethode
Kanssteekproef
Studie Bevolking
Participants in the main AIM-HIGH study (NCT00120289)
Beschrijving
Inclusion Criteria:
- Eligible for main AIM-HIGH study (NCT00120289)
- Medically able to undergo MRI procedure
- Willing to provide informed consent for participation in this substudy
Exclusion Criteria:
- Uses pacemaker or has metallic implants
- History of bilateral carotid endarterectomy
- Glomerular filtration rate less than 60 mL/min/1.73 m^2
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Observatiemodellen: Cohort
- Tijdsperspectieven: Prospectief
Cohorten en interventies
Groep / Cohort |
Interventie / Behandeling |
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Simvastatine
Deelnemers aan het hoofdonderzoek van AIM-HIGH die simvastatine krijgen.
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Participants will be enrolled in this substudy only if they are candidates for the main AIM-HIGH study (NCT00120289).
Participants will be randomly assigned to simvastatin or simvastatin plus niacin as a part of the main AIM-HIGH protocol, and adjustments in simvastatin and/or niacin doses will be made as per the protocol for the main AIM-HIGH study.
Andere namen:
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Simvastatine en niacine met verlengde afgifte
Deelnemers aan het hoofdonderzoek van AIM-HIGH die simvastatine en niacine met verlengde afgifte krijgen.
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Participants will be enrolled in this substudy only if they are candidates for the main AIM-HIGH study (NCT00120289).
Participants will be randomly assigned to simvastatin or simvastatin plus niacin as a part of the main AIM-HIGH protocol, and adjustments in simvastatin and/or niacin doses will be made as per the protocol for the main AIM-HIGH study.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Mean plaque lipid composition in carotid arteries assessed by MR
Tijdsspanne: Through 24Months post AIM-HIGH Randomization
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To test the primary hypothesis that compared with LDL-lowering alone, intensive LDL-lowering plus HDL-raising therapy decreases the mean plaque lipid composition in carotid arteries assessed by MRI.
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Through 24Months post AIM-HIGH Randomization
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Additional plaque characteristics as assessed by MRI
Tijdsspanne: Through 24Months post AIM-HIGH Randomization
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To test the additional hypotheses regarding plaque burden, plaque lipid depletion time course, association with cardiovascular event risk and lipid characteristics.
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Through 24Months post AIM-HIGH Randomization
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
- Hippe DS, Phan BAP, Sun J, Isquith DA, O'Brien KD, Crouse JR, Anderson T, Huston J, Marcovina SM, Hatsukami TS, Yuan C, Zhao XQ. Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Disease on Intensive Lipid Therapy: An Analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Carotid Magnetic Resonance Imaging Substudy-Brief Report. Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):673-678. doi: 10.1161/ATVBAHA.117.310368. Epub 2018 Jan 4.
- Sun J, Zhao XQ, Balu N, Hippe DS, Hatsukami TS, Isquith DA, Yamada K, Neradilek MB, Canton G, Xue Y, Fleg JL, Desvigne-Nickens P, Klimas MT, Padley RJ, Vassileva MT, Wyman BT, Yuan C. Carotid magnetic resonance imaging for monitoring atherosclerotic plaque progression: a multicenter reproducibility study. Int J Cardiovasc Imaging. 2015 Jan;31(1):95-103. doi: 10.1007/s10554-014-0532-7. Epub 2014 Sep 13.
- Chen H, Sun J, Kerwin WS, Balu N, Neradilek MB, Hippe DS, Isquith D, Xue Y, Yamada K, Peck S, Yuan C, O'Brien KD, Zhao XQ. Scan-rescan reproducibility of quantitative assessment of inflammatory carotid atherosclerotic plaque using dynamic contrast-enhanced 3T CMR in a multi-center study. J Cardiovasc Magn Reson. 2014 Aug 1;16(1):51. doi: 10.1186/s12968-014-0051-7.
- Zhao XQ, Hatsukami TS, Hippe DS, Sun J, Balu N, Isquith DA, Crouse JR 3rd, Anderson T, Huston J 3rd, Polissar N, O'Brien K, Yuan C; AIM-HIGH Carotid MRI Sub-study Investigators. Clinical factors associated with high-risk carotid plaque features as assessed by magnetic resonance imaging in patients with established vascular disease (from the AIM-HIGH Study). Am J Cardiol. 2014 Nov 1;114(9):1412-9. doi: 10.1016/j.amjcard.2014.08.001. Epub 2014 Aug 13.
- Zhao XQ, Sun J, Hippe DS, Isquith DA, Canton G, Yamada K, Balu N, Crouse JR 3rd, Anderson TJ, Huston J 3rd, O'Brien KD, Hatsukami TS, Yuan C; AIM-HIGH Carotid MRI Substudy Investigators. Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH. Circ Cardiovasc Imaging. 2022 Nov;15(11):e014229. doi: 10.1161/CIRCIMAGING.122.014229. Epub 2022 Nov 15.
- O'Brien KD, Hippe DS, Chen H, Neradilek MB, Probstfield JL, Peck S, Isquith DA, Canton G, Yuan C, Polissar NL, Zhao XQ, Kerwin WS. Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging. Atherosclerosis. 2016 Feb;245:74-81. doi: 10.1016/j.atherosclerosis.2015.11.032. Epub 2015 Dec 1.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 maart 2008
Primaire voltooiing (Werkelijk)
1 april 2013
Studie voltooiing (Werkelijk)
1 februari 2015
Studieregistratiedata
Eerst ingediend
5 augustus 2010
Eerst ingediend dat voldeed aan de QC-criteria
6 augustus 2010
Eerst geplaatst (Schatting)
10 augustus 2010
Updates van studierecords
Laatste update geplaatst (Werkelijk)
9 februari 2018
Laatste update ingediend die voldeed aan QC-criteria
7 februari 2018
Laatst geverifieerd
1 februari 2018
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Myocardiale ischemie
- Hartziekten
- Hart-en vaatziekten
- Vaatziekten
- Cerebrovasculaire aandoeningen
- Hersenziekten
- Ziekten van het centrale zenuwstelsel
- Ziekten van het zenuwstelsel
- Arteriosclerose
- Arteriële occlusieve ziekten
- Hart-en vaatziekte
- Coronaire hartziekte
- Ziekten van de halsslagader
- Atherosclerose
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Vaatverwijdende middelen
- Enzymremmers
- Antimetabolieten
- Micronutriënten
- Middelen tegen cholesterol
- Hypolipidemische middelen
- Vetregulerende middelen
- Hydroxymethylglutaryl-CoA-reductaseremmers
- Vitaminen
- Vitamine B-complex
- Nicotinezuren
- Simvastatine
- Niacinamide
- Niacine
Andere studie-ID-nummers
- 627
- R01HL088214 (Subsidie/contract van de Amerikaanse NIH)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .