Inflammation and Coronary Endothelial Function

• Status: Completed
• Trial end date: 2020-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Anti-Inflammatory Agents; Colchicine; Methotrexate

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.