Effects of IL-1 Beta Inhibition on Vascular Inflammation in TET2 Clonal Hematopoiesis

Prior treatment

• placement of a drug-eluting stent in a proximal coronary arterial segment \<180 days before baseline imaging
• prior coronary artery bypass grafting
• current treatment with prescription, systemic (oral, IV \[intravenous\], or IM \[intramuscular\]) steroids or anti-inflammatory/immune suppressant medical therapies (including colchicine but excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases, post-transplant care, asthma, or pain
• use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for \>7 days within the past 1 month
• use of IV or IM steroids or IV or IM anti-inflammatory/immune suppressant medication within the past 3 months
• use of phosphodiesterase type 5 inhibitor AND refusal to abstain from use of these medications within the 5 days prior to scheduled CCTA scan
• significant radiation exposure (40msV) received within the past 12 months
• concurrent enrollment in another research study judged by the investigators to interfere with the current study
• live vaccinations within 3 months prior to randomization visit or live vaccinations planned during the trial

Other illness

• history of blood malignancy or current solid-tumor malignancy
• history of organ or stem cell transplantation
• known allergy to dextran's and/or DTPA and/or radiometals and/or severe allergy to iodinated contrast media
• history or evidence of tuberculosis (TB) (active or latent) infection or risk factor for TB
• active bacterial, fungal or viral infection at the time of enrollment or history of recurrent infections

Lab values

• estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73 m2
• known active or recurrent hepatic disease (including cirrhosis or ALT/AST levels \>3 times the upper limit oof or total bilirubin \>2 times the upper limits of normal)

Other

• pregnancy or breastfeeding
• contraindications to nitroglycerin known narrow angle glaucoma, or known severe aortic stenosis
• suspected or proven immunocompromised state

• 18 years or older
• Coronary artery disease, defined as prior heart attack, coronary stent procedure \>180 days before baseline imaging, or advanced subclinical coronary atherosclerosis (coronary artery calcium score ≥300 Agatston units, CAD-RADS 3 or greater atherosclerosis on coronary CT angiography, or qualitatively severe coronary artery calcification identified on non-gated CT imaging)
• Presence of either TET2 mutations or no myeloid driver mutations on prior sequencing
• TET2-mutant myelodysplastic syndrome (MDS) or dysplastic-type chronic myelomonocytic leukemia (CMML) participants only must meet all of the following criteria:
  • Very low, low, or moderate-low risk for disease progression according to IPSS-M (score ≤0)
  • Peripheral blood blasts \<2% and bone marrow blasts \<5%
  • WBC \<13 ×10⁹/L
  • ANC ≥1.0 ×10⁹/L
  • Hemoglobin ≥10 g/dL
  • Platelet count ≥50 ×10⁹/L
  • No clinically significant transfusion requirement attributable to MDS/CMML, defined as receipt of \<2 units of RBCs and no platelet transfusions during the 8 weeks preceding screening (excluding transfusions for acute bleeding, surgery, or another transient intercurrent condition)
  • In the judgment of the treating oncologist, clinically stable disease for which disease-modifying therapy is not anticipated to be required within the subsequent 24 months