This early phase I trial studies the effects of combination of omeprazole and low dose aspirin to identify colorectal (CRC) biomarkers to prevent the recurrence of colorectal polyps in people with a history of multiple polyps or an incompletely removed polyp. A biomarker is something that can be measured in tissue, blood or other body fluids. Some biomarkers measure how healthy the tissue is. Other biomarkers measure changes that could lead to abnormal processes or conditions in the future. Omeprazole works to reduce the amount of acid the stomach produces, and also contributes to other effects, such as inhibition of fatty acid synthase. Aspirin is part of the non-steroidal anti-inflammatory drug (NSAID) family, which are drugs routinely used for their pain-killing, fever-reducing, or anti-inflammatory properties. The information gained from this study could help researchers determine if giving omeprazole and low dose aspirin affects abnormal changes in colorectal cells to prevent the recurrence of colorectal polyps.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06378398.
PRIMARY OBJECTIVE:
I. To identify biomarkers for omeprazole/aspirin combination treatment in the human colorectum to enable subsequent phase 1 and 2 trials.
SECONDARY OBJECTIVE:
I. To evaluate similarities in gene expression changes by the preventive agents in human colon with that in the rodent colon using ribonucleic acid sequencing (RNA-seq) data generated in the Rao laboratory.
EXPLORATORY OBJECTIVES:
I. To compare pre-treatment biomarkers between pathological categories of lesions (villous, tubular and mixed adenomas, and serrated lesions) and changes in the different subtypes of lesion post-treatment.
II. To compare gene signature in colonic lesions from the most recent standard of care colonoscopy that are stored in paraffin blocks with the colonic lesions collected at the research flexible sigmoidoscopy to determine if the stored samples would suffice for use as a pre-treatment tissue samples in future studies.
III. To collect sufficient bio-samples for future, additional assays. These include:
IIIa. Verification of large changes in gene expression from transcriptomic assays with proteomic or immunohistochemical assays;
IIIb. Lipidomic studies of colon tissue since aspirin and omeprazole are both expected to affect lipid metabolism in colon tissue. This will include products from cyclooxygenase, lipoxygenase and cytochrome P450- mediated metabolism of arachidonic acid, many of which are known to be associated with increased or decreased risks of CRC;
IIIc. Biomarkers of fatty acid synthase inhibition in colonic tissue pre/post and analyze the results by obesity status. This will include fatty acid profiles;
IIId. To quantify systemic biomarkers of inflammatory stress (plasma c-reactive protein (CRP), IL-6, IL1b, IIL-10, TNFalpha) since both test agents reduce inflammatory stress;
IIIe. To quantify urinary PGE-M, a stable metabolite of PGE2, a major pro-inflammatory pathway that is inhibited by aspirin PGE-M, can serve as a non-invasive biomarker of aspirin efficacy for inhibiting prostanoid production even when low doses of aspirin are used. This then makes it possible to non-invasively measure aspirin effects in each person;
IIIf. To evaluate changes in the mucosal-adherent microbiome in colonic biopsies of normal mucosa and to explore if inter-individual difference in microbiome composition contribute to inflammatory stress.
OUTLINE:
Patients receive omeprazole orally (PO) once daily (QD) and aspirin PO QD for 25-45 days with a desired target of 28 days. Patients also undergo colonoscopy or sigmoidoscopy, biopsy, and blood and urine sample collection on study.
After completion of study treatment, patients are followed up to 30 days.
Lead OrganizationUniversity of Michigan Rogel Cancer Center
Principal InvestigatorElena Martinez Stoffel
