Carotid Plaque Characteristics by MRI in AIM-HIGH (Carotid MRI Substudy)
7 febbraio 2018 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Osservativo
Iscrizione (Effettivo)
230
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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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, Stati Uniti, 85032
- Cardiovascular Consultants
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California
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Long Beach, California, Stati Uniti, 90822
- Long Beach VA Medical Center
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Los Angeles, California, Stati Uniti, 90033
- University of Southern California
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Maryland
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Baltimore, Maryland, Stati Uniti, 21201
- University of Maryland
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Baltimore, Maryland, Stati Uniti, 21205
- Johns Hopkins University
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Minnesota
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Rochester, Minnesota, Stati Uniti, 55905
- Mayo Clinic
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North Carolina
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Durham, North Carolina, Stati Uniti, 27710
- Duke University
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Winston-Salem, North Carolina, Stati Uniti, 27157
- Wake Forest University
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti, 19104
- Philadelphia VA Medical Center
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Texas
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Houston, Texas, Stati Uniti, 77030
- Baylor College of Medicine
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Houston, Texas, Stati Uniti, 77030
- Methodist Hospital
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Houston, Texas, Stati Uniti, 77030
- Kelsey Research Foundation
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Washington
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Seattle, Washington, Stati Uniti, 98104
- Harborview Medical Center
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Seattle, Washington, Stati Uniti, 98105
- University of Washington
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Seattle, Washington, Stati Uniti, 98108
- Puget Sound VA Medical Center, Seattle Campus
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
45 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Metodo di campionamento
Campione di probabilità
Popolazione di studio
Participants in the main AIM-HIGH study (NCT00120289)
Descrizione
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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Modelli osservazionali: Coorte
- Prospettive temporali: Prospettiva
Coorti e interventi
Gruppo / Coorte |
Intervento / Trattamento |
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Simvastatina
Partecipanti allo studio principale AIM-HIGH che stanno ricevendo simvastatina.
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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.
Altri nomi:
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Simvastatina e niacina a rilascio prolungato
Partecipanti allo studio principale AIM-HIGH che stanno ricevendo simvastatina e niacina a rilascio prolungato.
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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.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Mean plaque lipid composition in carotid arteries assessed by MR
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Additional plaque characteristics as assessed by MRI
Lasso di tempo: 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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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- 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.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 marzo 2008
Completamento primario (Effettivo)
1 aprile 2013
Completamento dello studio (Effettivo)
1 febbraio 2015
Date di iscrizione allo studio
Primo inviato
5 agosto 2010
Primo inviato che soddisfa i criteri di controllo qualità
6 agosto 2010
Primo Inserito (Stima)
10 agosto 2010
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
9 febbraio 2018
Ultimo aggiornamento inviato che soddisfa i criteri QC
7 febbraio 2018
Ultimo verificato
1 febbraio 2018
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Ischemia miocardica
- Malattie cardiache
- Malattia cardiovascolare
- Malattie vascolari
- Disturbi cerebrovascolari
- Malattie del cervello
- Malattie del sistema nervoso centrale
- Malattie del sistema nervoso
- Arteriosclerosi
- Malattie arteriose occlusive
- Malattia coronarica
- Disfunsione dell'arteria coronaria
- Malattie dell'arteria carotidea
- Aterosclerosi
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti vasodilatatori
- Inibitori enzimatici
- Antimetaboliti
- Micronutrienti
- Agenti anticolesteremici
- Agenti ipolipidemizzanti
- Agenti regolatori dei lipidi
- Inibitori dell'idrossimetilglutaril-CoA reduttasi
- Vitamine
- Complesso di vitamina B
- Acidi nicotinici
- Simvastatina
- Niacinammide
- Niacina
Altri numeri di identificazione dello studio
- 627
- R01HL088214 (Sovvenzione/contratto NIH degli Stati Uniti)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .