Inflammation and Coronary Endothelial Function
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Inflammation
Intervention: Methotrexate; Colchicine; Placebo
Intervention description: Administered to determine the effect of anti-inflammatory agents on coronary and systemic endothelial function in patients with coronary artery disease; Administered to determine the effect of anti-inflammatory agents on coronary and systemic endothelial function in patients with coronary artery disease.; Prepared by Johns Hopkins Investigational Drug Service to mimic methotrexate and colchicine.
Intervention MeSH terms: Methotrexate; Colchicine
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 111.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

Summary:

      The investigators are studying whether anti-inflammatory agents can improve abnormal coronary
      artery function in patients with coronary artery disease (CAD) and abnormal coronary artery
      endothelial function.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants of either gender who are 21 years of age (no upper age limit),

          -  History of prior Myocardial Infarction (MI), coronary revascularization, or coronary
             angiography or Multidetector Computer Tomography (MDCT) demonstrating at least one
             coronary artery with >50% luminal stenosis and no plans for revascularization,

          -  Clinically stable for 3 months,

          -  Vascular inflammation based on elevated hsCRP (>2mg L-1), or a clinical diagnosis of
             diabetes mellitus or metabolic syndrome (metabolic syndrome is defined by three or
             more of the following): Abdominal obesity (waist circumference: Men>102 cm (>40 in),
             Women >88 cm (>35 in)), Serum triglycerides ≥150 mg/dL (or taking medication to treat
             high triglycerides), HDL cholesterol: Men<40 mg/dL, Women<50 mg/dL (or taking
             medication to treat low HDL cholesterol), High blood pressure: ≥130/≥85 mm Hg (or
             taking medication to treat high blood pressure), or Fasting glucose: ≥100 mg/dL (or
             taking medication to treat high fasting glucose).

          -  Abnormal Coronary Endothelial Function (CEF) (change in CSA during IHE of <0% of the
             resting value: by this we mean any decrease in CSA or no change (0%) from baseline
             during IHE),

          -  Permission of patient's clinical attending physician,

          -  Patients being treated with a statin.

        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,

          -  Acute coronary syndrome within the prior three months,

          -  Pregnant women,

          -  Contraindications to methotrexate or colchicine as outlined by the American College of
             Rheumatology; including active bacterial infection, tuberculosis, or herpes zoster
             infection, leukopenia (<4000/mm3), thrombocytopenia (<135,000/mm3), elevation in
             hepatic transaminases (>2x upper limit of normal), hepatitis B or C, moderate renal
             disease (estimated creatine clearance <45ml/min), or planned surgery,

          -  Chronic inflammatory condition such as lupus or rheumatoid arthritis, ulcerative
             colitis or Crohn's disease,

          -  Interstitial lung disease or pulmonary fibrosis,

          -  HIV positive,

          -  Requirement for, or intolerance to, methotrexate or colchicine ,

          -  Intolerance to methotrexate, colchicine or folate,

          -  History of non-basal cell malignancy or treatment for lymphoproliferative disease in
             the past 5 years,

          -  Requirement for use of drugs that alter folate metabolism,

          -  History of alcohol abuse or unwillingness to limit consumption to < 4 drinks per week,

          -  Women of childbearing potential or intention to breastfeed.

          -  Men who plan to father children during the study period; men who have sexual
             intercourse with women of childbearing potential must agree to use a condom,

          -  Chronic use of oral or IV steroid therapy or other immunosuppressive or biologic
             response modifiers,

          -  History of chronic pericardial effusion, pleural effusion or ascites,

          -  New York Heart Association Class IV heart failure.