دورية أكاديمية
أعرض في EDS

No benefit of HDL mimetic CER-001 on carotid atherosclerosis in patients with genetically determined very low HDL levels.

التفاصيل البيبلوغرافية
العنوان: No benefit of HDL mimetic CER-001 on carotid atherosclerosis in patients with genetically determined very low HDL levels.
المؤلفون: Zheng KH; Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands., Kaiser Y; Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands., van Olden CC; Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands., Santos RD; Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil; Hospital Israelita Albert Einstein, Sao Paulo, Brazil., Dasseux JL; Cerenis Therapeutics, Labège, Toulouse, France., Genest J; Department of Medicine, Division of Cardiology, McGill University, Montréal, Quebec, Canada., Gaudet D; Department of Medicine, Université de Montréal, Chicoutimi, Quebec, Canada., Westerink J; Department of Vascular Medicine, Utrecht University Medical Center, Utrecht, the Netherlands., Keyserling C; Cerenis Therapeutics, Labège, Toulouse, France., Verberne HJ; Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands., Leitersdorf E; Center for Research, Prevention and Treatment of Atherosclerosis, Hadassah Hebrew University Medical Center, Jerusalem, Israel., Hegele RA; Robarts Research Institute, Western University, London, Ontario, Canada., Descamps OS; Centres Hospitaliers Jolimont, La Louvière, Belgium., Hopkins P; University of Utah, Salt Lake City, UT, USA., Nederveen AJ; Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands., Stroes ESG; Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands. Electronic address: e.s.stroes@amsterdamumc.nl.
المصدر: Atherosclerosis [Atherosclerosis] 2020 Oct; Vol. 311, pp. 13-19. Date of Electronic Publication: 2020 Aug 29.
نوع المنشور: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Ireland NLM ID: 0242543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1484 (Electronic) Linking ISSN: 00219150 NLM ISO Abbreviation: Atherosclerosis Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier
Original Publication: Amsterdam, Elsevier.
مواضيع طبية MeSH: Carotid Artery Diseases*/diagnostic imaging , Carotid Artery Diseases*/drug therapy , Lipoproteins, HDL*, Apolipoprotein A-I ; Cholesterol, HDL ; Humans ; Middle Aged ; Phospholipids ; Positron Emission Tomography Computed Tomography ; Recombinant Proteins
مستخلص: Background and Aims: Infusion of high-density lipoprotein (HDL) mimetics failed to induce regression of atherosclerosis in recent randomized clinical trials. However, patients in these previous trials had normal levels of HDL-cholesterol, which potentially limited efficacy. Patients with very low levels of HDL-cholesterol and impaired cholesterol efflux capacity can be expected to derive the most potential benefit from infusion of HDL mimetics. This randomized clinical trial evaluated the efficacy of infusions of the HDL mimetic CER-001 in patients with genetically determined very low levels of HDL cholesterol.
Methods: In this multicenter, randomized clinical trial, we recruited patients with familial hypoalphalipoproteinemia (due to ABCA1 and/or APOA1 loss-of-function variants). Participants were randomized to intravenous infusions of 8 mg/kg CER-001 or placebo (2:1 ratio), comprising 9 weekly infusions followed by infusions every two weeks. Patients underwent repeated 3T-MRI to assess mean vessel wall area and 18 F-FDG PET/CT to quantify arterial wall inflammation.
Results: A total of 30 patients with a mean age of 52.7 ± 7.4 years and HDL-cholesterol of 0.35 ± 0.25 mmol/L were recruited. After 24 weeks, the absolute change in mean vessel wall area was not significantly different in the CER-001 group compared with placebo (n = 27; treatment difference: 0.77 mm 2 , p = 0.21). Furthermore, there was no significant difference in carotid arterial wall inflammation (n = 24, treatment difference: 0.10 target-to-background ratio of the most diseased segment, p = 0.33) after 24 weeks.
Conclusion: In patients with genetically determined very low HDL-cholesterol, 24 weeks of treatment with HDL mimetic CER-001 did not reduce carotid vessel wall dimensions or arterial wall inflammation, compared with placebo.
(Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: CER-001; Familial hypoalphalipoproteinemia; HDL; MRI; PET/CT; Randomized clinical trial
المشرفين على المادة: 0 (Apolipoprotein A-I)
0 (CER-001)
0 (Cholesterol, HDL)
0 (Lipoproteins, HDL)
0 (Phospholipids)
0 (Recombinant Proteins)
تواريخ الأحداث: Date Created: 20200912 Date Completed: 20210623 Latest Revision: 20210623
رمز التحديث: 20221213
DOI: 10.1016/j.atherosclerosis.2020.08.004
PMID: 32919280
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-1484
DOI:10.1016/j.atherosclerosis.2020.08.004