Inflammatory Pathogenesis of Coronary Atherosclerosis in HIV

NCT02624180 | Completed Phase 2 Results DMC

• 2 other identifiers: IRB000708921R01HL125059
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

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).

Conditions

Coronary Artery Disease; Human Immunodeficiency Virus

Outcome Measures

Primary Outcomes (1)

• Coronary Endothelial Function Measured by Percent Change in Coronary Blood Flow With Exercise (%) 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 Outcomes (8)

• Coronary Endothelial Function at 24 Weeks;

  At 24 weeks.

• Change in Coronary Artery Cross-sectional Area (CSA) 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

  At 24 weeks

• High-sensitivity C-reactive Protein (hsCRP) at 8 Weeks.

  At 8 weeks.

• Brachial Flow Mediated Dilatation (FMD) at 8 Weeks.

  At 8 weeks

Study Arms (2)

Colchicine

EXPERIMENTAL

Colchicine 0.6 mg daily by mouth

Drug: Colchicine

Placebo

PLACEBO COMPARATOR

Placebo for colchicine 1 tablet by mouth daily

Drug: Placebo

Interventions

Colchicine DRUG

Administered to determine the effect of anti-inflammatory agents on coronary and systemic endothelial function in patients with coronary artery disease.

Also known as: Colcrys

Colchicine

Placebo DRUG

A substance containing no medication

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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,

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (9)

• 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.

  PMID: 17353456 BACKGROUND

• 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.

  PMID: 14522472 BACKGROUND

• 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.

  PMID: 21050976 BACKGROUND

• 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.

  PMID: 23536782 BACKGROUND

• 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.

  PMID: 22492483 BACKGROUND

• 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.

  PMID: 23265346 BACKGROUND

• 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.

  PMID: 6426817 BACKGROUND

• 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.

  PMID: 36634369 DERIVED

• 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.

  PMID: 33587443 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Acquired Immunodeficiency Syndrome

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Robert G. Weiss, MD
• Organization: Johns Hopkins Hospital

rweiss@jhmi.edu

410-955-1703

Study Officials

• Robert G Weiss, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2015
• First Posted: December 8, 2015
• Study Start: November 1, 2015
• Primary Completion: August 1, 2020
• Study Completion: September 1, 2020
• Last Updated: October 21, 2021
• Results First Posted: August 19, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)