Inflammatory Pathogenesis of Coronary Atherosclerosis in HIV
NCT ID: NCT02624180
Last Updated: 2021-10-21
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
81 participants
INTERVENTIONAL
2015-11-30
2020-09-01
Brief Summary
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Detailed Description
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What the investigators are studying in this program is the function of the coronary arteries and in particular the inner lining of the arteries called the endothelium in patients with HIV. The endothelium has several important functions; one of them is that under conditions of stress it releases a substance called nitric oxide which increases the size of the artery and increases blood flow. When it is not functioning normally the artery does not increase as much and blood flow does not increase during stress.
The investigators study coronary artery function with magnetic resonance imaging, or MRI. MRI is a method of obtaining images of what is happening inside the body. MRI does not involve radiation, x-ray, or injection of contrast. The investigators can measure flow in the artery and the dimension of the artery at rest and with a handgrip stress and learn the extent to which the artery dilates and flow increases with the stress. The investigators believe that inflammation can interfere with normal function and that by decreasing inflammation abnormal endothelial function may be improved.
Colchicine is an anti-inflammatory agent approved by the Food and Drug Administration (FDA) to treat arthritis and some other conditions. This drug is not approved for use to suppress inflammation in patients with coronary artery disease and improve coronary artery endothelial function. The FDA is allowing the use of colchicine or a placebo in this research study.
This study will involve 24 weeks of colchicine or placebo and 3 Magnetic Resonance Imaging (MRI) scans of the heart and other study procedures.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
OTHER
QUADRUPLE
Study Groups
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Colchicine
Colchicine 0.6 mg daily by mouth
Colchicine
Administered to determine the effect of anti-inflammatory agents on coronary and systemic endothelial function in patients with coronary artery disease.
Placebo
Placebo for colchicine 1 tablet by mouth daily
Placebo
A substance containing no medication
Interventions
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Colchicine
Administered to determine the effect of anti-inflammatory agents on coronary and systemic endothelial function in patients with coronary artery disease.
Placebo
A substance containing no medication
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* HIV viral load \<100 copies/mL (plasma HIV RNA concentration),
* Abnormal CEF at baseline (\<7ml/min change in CBF during IHE as compared to resting value).
Exclusion Criteria
* Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips) or indwelling metallic projectiles,
* History of clinical CAD, including acute coronary syndrome, myocardial infarction or revascularization,
* Resting ECG with evidence of Q wave myocardial infarction,
* Pregnant women,
* Recent history, within the past 3 months, of cocaine or heroin use,
* Moderate or greater renal impairment (estimated glomerular filtration rate \<45ml/min),
* Moderate-severe hepatic disease (elevation in hepatic transaminases \>3x upper limit of normal),
* Leukopenia (\<3000/mm3) or thrombocytopenia (\<100,000/mm3),
* CD4\<200 cell/mm3,
* Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative colitis or Crohn's disease,
* Requirement for, or intolerance to, colchicine,
* Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed,
* Chronic, continuous use of oral or IV steroid therapy or other immunosuppressive or biologic response modifiers or anti-inflammatory agents (chronic NSAIDs or acetylsalicylic acid (ASA) \>81mg daily),
* History of chronic pericardial effusion, pleural effusion, ascites or peripheral neuropathy manifested by both signs and symptoms,
* Taking protease inhibitors (PI), cobicistat, or CYP3A4 inhibitors.
21 Years
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
Johns Hopkins University
OTHER
Responsible Party
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Principal Investigators
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Robert G Weiss, MD
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins University
Locations
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Johns Hopkins Hospital
Baltimore, Maryland, United States
Countries
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References
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Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007 Mar 13;115(10):1285-95. doi: 10.1161/CIRCULATIONAHA.106.652859. No abstract available.
Widlansky ME, Gokce N, Keaney JF Jr, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003 Oct 1;42(7):1149-60. doi: 10.1016/s0735-1097(03)00994-x.
Hays AG, Hirsch GA, Kelle S, Gerstenblith G, Weiss RG, Stuber M. Noninvasive visualization of coronary artery endothelial function in healthy subjects and in patients with coronary artery disease. J Am Coll Cardiol. 2010 Nov 9;56(20):1657-65. doi: 10.1016/j.jacc.2010.06.036.
Hays AG, Stuber M, Hirsch GA, Yu J, Schar M, Weiss RG, Gerstenblith G, Kelle S. Non-invasive detection of coronary endothelial response to sequential handgrip exercise in coronary artery disease patients and healthy adults. PLoS One. 2013;8(3):e58047. doi: 10.1371/journal.pone.0058047. Epub 2013 Mar 11.
Hays AG, Kelle S, Hirsch GA, Soleimanifard S, Yu J, Agarwal HK, Gerstenblith G, Schar M, Stuber M, Weiss RG. Regional coronary endothelial function is closely related to local early coronary atherosclerosis in patients with mild coronary artery disease: pilot study. Circ Cardiovasc Imaging. 2012 May 1;5(3):341-8. doi: 10.1161/CIRCIMAGING.111.969691. Epub 2012 Apr 5.
Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013 Jan 29;61(4):404-410. doi: 10.1016/j.jacc.2012.10.027. Epub 2012 Dec 19.
Brown BG, Lee AB, Bolson EL, Dodge HT. Reflex constriction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exercise. Circulation. 1984 Jul;70(1):18-24. doi: 10.1161/01.cir.70.1.18.
Bagchi S, Kwapong YA, Schar M, Bonanno G, Streeb V, Lai S, Gerstenblith G, Weiss RG, Hays AG. The Relationship Between Impaired Coronary Endothelial Function and Systemic Markers of Inflammation in People Living With HIV. J Acquir Immune Defic Syndr. 2023 May 1;93(1):47-54. doi: 10.1097/QAI.0000000000003162.
Hays AG, Schar M, Barditch-Crovo P, Bagchi S, Bonanno G, Meyer J, Afework Y, Streeb V, Stradley S, Kelly S, Anders NM, Margolick JB, Lai S, Gerstenblith G, Weiss RG. A randomized, placebo-controlled, double-blinded clinical trial of colchicine to improve vascular health in people living with HIV. AIDS. 2021 Jun 1;35(7):1041-1050. doi: 10.1097/QAD.0000000000002845.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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IRB00070892
Identifier Type: -
Identifier Source: org_study_id