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Omeprazole and Low Dose Aspirin to Identify Colorectal Biomarkers of Preventive Efficacy
Trial Status: active
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.
Inclusion Criteria
Age 18-75
Individuals who are due for a standard of care colonoscopy
Have a prior history of colorectal neoplasia including any one of the following:
* Multiple (>= 5) colorectal adenomas on most recent colonoscopy
* Multiple (>= 5) sessile serrated polyps on most recent colonoscopy
* Adenomatous polyps meeting criteria for colon polyposis of unknown etiology (>= 20 lifetime adenomas)
* Serrated polyps meeting criteria for serrated polyposis syndrome
* History of incompletely resected colorectal polyp(s) (adenoma or sessile serrated polyp) on most recent colonoscopy
Willing to avoid taking non-steroidal anti-inflammatory drugs that are not provided by the study in the 30 days prior to visit 1 and while on study
Willing to avoid taking proton pump inhibitors that are not provided by the study in the 30 days prior to visit 1 and while on study
Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation since endoscopy is not recommended during pregnancy
Absolute neutrophil count >= 1,000/microliter (within the last 60 days)
Platelets >= 100,000/microliter (within the last 60 days)
Total bilirubin =< 1.5 fold of the institutional upper limit of normal (within the last 60 days)
Note: Higher total bilirubin levels (=< 3 mg/dL) can be allowed if due to known benign liver condition such as Gilbert's
Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 fold of the institutional upper limit of normal (within the last 60 days)
Creatinine =< 1.5 fold of the institutional upper limit of normal (within the last 60 days)
Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
Age 76 or higher since there is an increased risk of gastrointestinal (GI) bleeding and peptic ulcer disease in persons above 75 years of age
Pathogenic germline variants in adenomatous polyposis coli (APC) and deoxyribonucleic acid (DNA) mismatch repair (MMR) genes associated with Lynch Syndrome, or biallelic pathogenic germline variants in the MutY homologue glycosylase (MUTYH) gene
Have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to proton pump inhibitors and/or aspirin
Participants may not be receiving any other investigational agents
Have a history of prior aspirin or NSAID gastritis with bleeding
Currently taking a proton pump inhibitor and unable/unwilling to discontinue use 30 days prior to visit 1
Taking NSAIDs or aspirin > 25% of the time (> 8 days/month) and unable/unwilling to discontinue use 30 days prior to visit 1 and until visit 4
Currently taking medications associated with increased risk for bleeding (warfarin, Eliquis, Plavix, etc.)
Currently taking medications that have interactions with omeprazole: atazanavir, erlotinib, levoketoconazole, nelfinavir, pazopanib, rilpivirine, sparsentan, certain azole antifungals (itraconazole, ketoconazole, and posaconazole)
Have a history of hemophilia, Von Willebrand disease or any other known bleeding diathesis
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Individuals who the site physician investigator assesses as at high risk for bleeding due to heavy alcohol use or comorbid conditions
Pregnant women are excluded since endoscopy is not recommended while pregnant
Have invasive cancer or being treated for invasive cancer at the current time or within the past 36 months, with the exception of cancers curatively removed by surgery, other than melanoma, and stage I and II cervical squamous cell cancers
Additional locations may be listed on ClinicalTrials.gov for NCT06378398.
Locations matching your search criteria
United States
Michigan
Ann Arbor
University of Michigan Comprehensive Cancer Center
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.
Trial PhasePhase I
Trial Typeprevention
Lead OrganizationUniversity of Michigan Comprehensive Cancer Center
