Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis

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PRIMARY OBJECTIVE: I. To determine the effect of atorvastatin calcium (atorvastatin) treatment on reducing the fraction of colonic epithelial cells expressing mutant p53 protein detected via immunohistochemical staining in biopsy samples of colorectal mucosa obtained during colonoscopies done before...

PRIMARY OBJECTIVE: I. To determine the effect of atorvastatin calcium (atorvastatin) treatment on reducing the fraction of colonic epithelial cells expressing mutant p53 protein detected via immunohistochemical staining in biopsy samples of colorectal mucosa obtained during colonoscopies done before and after atorvastatin intervention and compared to placebo control. SECONDARY OBJECTIVES: I. Examination of the effect of atorvastatin on the levels of biomarkers including Ki-67 (cell proliferation), Waf1p21 (wild type p53 allele reactivated signal), and cleaved caspase-3 (wild type p53-induced cell apoptosis) using immunohistochemistry (IHC) approach for colorectal biopsy specimens. II. Examination of the effect of atorvastatin on the spectrum, hotspot and load of TP53 gene mutations using next generation sequencing and droplet digital polymerase chain reaction (PCR). III. Examination of the effect of atorvastatin on the severity of histologic inflammation in colorectal biopsies using the Geboes grading system. IV. Examination of the effect of atorvastatin on the plasma concentration of cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) for monitoring atorvastatin effect on lowering cholesterol and its correlation with the levels of biomarkers in the colorectal biopsies. V. Examination of the effect of atorvastatin on the clinical efficacy on ulcerative colitis (UC) related symptoms using the Ulcerative Colitis Disease Activity Index (i.e. the Mayo score). VI. Will bank colorectal biopsies and blood samples and ribonucleic acid (RNA) and germline deoxyribonucleic acid (DNA) for future analyses, particularly on proteomics/prenylated protein profile, cytokine/chemokine profile, inflammatory lipid-mediator profile, RNA sequencing (RNAseq) and Chaperon/Co-chaperon proteins, etc. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive atorvastatin orally (PO) once daily (QD) for 12 months. ARM II: Patients receive placebo PO QD for 12 months. In both arms, patients also undergo collection of blood samples at each study visit to analyze the inflammation from the blood. After completion of study treatment, patients are followed up at 2 weeks.

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