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Inflammatory Pathogenesis of Coronary Atherosclerosis in HIV

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ClinicalTrials.gov Identifier: NCT02624180
Recruitment Status : Recruiting
First Posted : December 8, 2015
Last Update Posted : November 5, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Robert G. Weiss, Johns Hopkins University

Brief Summary:
The investigators are studying whether an anti-inflammatory intervention improves impaired coronary endothelial function (CEF) in HIV+ people with no clinical coronary artery disease (CAD).

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Human Immunodeficiency Virus Drug: Colchicine Drug: Placebo Phase 2

Detailed Description:

Survival in people with HIV has significantly improved with the use of antiretroviral therapy (ART) but HIV+ people now experience an increasing burden of chronic diseases, including coronary atherosclerosis and coronary artery disease (CAD). HIV patients manifest an increased risk of CAD and its consequences possibly due to interplay of inflammation with traditional risk factors (smoking, high cholesterol, and poor diet), some of the latter accentuated by ART.

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Inflammatory Pathogenesis of Coronary Atherosclerosis in HIV
Study Start Date : November 2015
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Colchicine

Arm Intervention/treatment
Experimental: Colchicine
Colchicine 0.6 mg daily by mouth
Drug: Colchicine
Administered to determine the effect of anti-inflammatory agents on coronary and systemic endothelial function in patients with coronary artery disease.
Other Name: Colcrys

Placebo Comparator: Placebo
Placebo for colchicine 1 tablet by mouth daily
Drug: Placebo
A substance containing no medication




Primary Outcome Measures :
  1. Coronary endothelial function at 8 weeks [ Time Frame: 8 weeks ]
    Change in coronary blood flow (CBF) from rest to that during isometric handgrip exercise (IHE) stress at 8 weeks.


Secondary Outcome Measures :
  1. Coronary endothelial function at 24 weeks; [ Time Frame: 24 weeks ]
    Change in coronary blood flow (CBF) from rest to that during isometric handgrip exercise (IHE) stress at 24 weeks.

  2. Change in coronary artery cross-sectional area (CSA) at 8 weeks [ Time Frame: 8 weeks ]
    Change in CSA as measured by the difference between CSA at rest and under IHE stress at 8 weeks

  3. Change in coronary artery cross-sectional area (CSA) at 24 weeks [ Time Frame: 24 weeks ]
    Change in CSA as measured by the difference between CSA at rest and under IHE stress at 24 weeks

  4. High-sensitivity C-reactive protein (hsCRP) at 8 and 24 weeks [ Time Frame: 8 to 24 weeks ]
  5. Brachial flow mediated dilatation (FMD) at 8 and 24 weeks [ Time Frame: 8 to 24 weeks ]
  6. Interleukin-6 (IL-6) at 8 and 24 weeks [ Time Frame: 8 and 24 weeks ]
  7. Change in hs-CRP at 8 and 24 weeks [ Time Frame: 8 and 24 weeks ]
    Change in hs-CRP as measured by the difference between baseline hs-CRP and week 8 hs-CRP or week 24 hs-CRP levels.

  8. Change in FMD at 8 and 24 weeks [ Time Frame: 8 and 24 weeks ]
    Change in FMD as measured by the difference between baseline FMD and week 8 FMD or week 24 FMD levels.

  9. Change in IL-6 at 8 and 24 weeks [ Time Frame: 8 and 24 weeks ]
    Change in IL-6 as measured by the difference between baseline IL-6 and week 8 IL-6 or week 24 IL-6 levels.



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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients of either gender who are 21 years of age (no upper age limit), HIV positive and taking stable ART (no change in ART regimen in last 3 months),
  • 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 unable to understand the risks, benefits, and alternatives of participation and give meaningful consent,
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02624180


Contacts
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Contact: Valerie Streeb, RN, BSN 4109551160 vstreeb1@jhmi.edu
Contact: Tricia Steinberg, RN, MSN 443-287-3469 asteinb3@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Tricia Steinberg, RN, MSN    443-287-3469    asteinb3@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Robert G Weiss, MD Johns Hopkins University

Publications:

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Responsible Party: Robert G. Weiss, Professor of Medicine and Radiology, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02624180     History of Changes
Other Study ID Numbers: IRB00070892
1R01HL125059 ( U.S. NIH Grant/Contract )
First Posted: December 8, 2015    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Immunologic Deficiency Syndromes
Atherosclerosis
Acquired Immunodeficiency Syndrome
HIV Infections
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Colchicine
Gout Suppressants
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents