Inflammatory Pathogenesis of Coronary Atherosclerosis in HIV

September 20, 2021 updated by: Johns Hopkins University
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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

81

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • Colcrys
Placebo Comparator: Placebo
Placebo for colchicine 1 tablet by mouth daily
Drug: Placebo
A substance containing no medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coronary Endothelial Function Measured by Percent Change in Coronary Blood Flow With Exercise (%) at 8 Weeks
Time Frame: Difference between measurements at baseline compared to measurement at 8 weeks
Percent change in coronary blood flow (CBF) from rest to that during isometric handgrip exercise (IHE) stress at 8 weeks.
Difference between measurements at baseline compared to measurement at 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coronary Endothelial Function at 24 Weeks;
Time Frame: At 24 weeks.
Change in coronary blood flow (CBF) from rest to that during isometric handgrip exercise (IHE) stress at 24 weeks.
At 24 weeks.
Change in Coronary Artery Cross-sectional Area (CSA) at 8 Weeks
Time Frame: Difference between measurements at baseline compared to measurement at 8 weeks
Change in CSA as measured by the difference between CSA at rest and under IHE stress at 8 weeks
Difference between measurements at baseline compared to measurement at 8 weeks
Change in Coronary Artery Cross-sectional Area (CSA) at 24 Weeks
Time Frame: At 24 weeks
Change in CSA as measured by the difference between CSA at rest and under IHE stress at 24 weeks
At 24 weeks
High-sensitivity C-reactive Protein (hsCRP) at 8 Weeks.
Time Frame: At 8 weeks.
High-sensitivity C-reactive protein (hsCRP) at 8 weeks
At 8 weeks.
Brachial Flow Mediated Dilatation (FMD) at 8 Weeks.
Time Frame: At 8 weeks
Brachial flow mediated dilatation (FMD) at 8 weeks.
At 8 weeks
Interleukin-6 (IL-6) at 8 Weeks
Time Frame: At 8 weeks
Interleukin-6 (IL-6) at 8 weeks
At 8 weeks
High-sensitivity C-reactive Protein (hsCRP) at 24 Weeks
Time Frame: At 24 weeks
High-sensitivity C-reactive Protein (hsCRP) at 24 weeks
At 24 weeks
Brachial Flow Mediated Dilatation (FMD) at 24 Weeks.
Time Frame: At 24 weeks
Brachial Flow Mediated Dilatation (FMD) at 24 Weeks.
At 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2015

Primary Completion (Actual)

August 1, 2020

Study Completion (Actual)

September 1, 2020

Study Registration Dates

First Submitted

November 11, 2015

First Submitted That Met QC Criteria

December 3, 2015

First Posted (Estimate)

December 8, 2015

Study Record Updates

Last Update Posted (Actual)

October 21, 2021

Last Update Submitted That Met QC Criteria

September 20, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00070892
  • 1R01HL125059 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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