This study is designed to test the use of Pyrvinium vs placebo as a treatment for gastric intestinal metaplasia with features associated with increased risk of cancer. Response will be determined by assessing the extent and quality of the gastric intestinal metaplasia before and after treatment.

A secondary aim will be to generate gastric organoids from patient-derived samples to test the effects of pyrvinium in vitro in patient-derived samples, and also to identify new drugs that may help reverse gastric intestinal metaplasia.

The proposed study is an early Phase II Clinical Trial designed to generate additional data regarding safety and efficacy for the use of Pyrvinium, an FDA-approved drug no longer in active use. The study design includes enrollment in an observational cohort for a research-focused screening upper endoscopy to document the extent and type of gastric intestinal metaplasia in patients previously diagnosed with this condition using a standardized mapping protocol (as described below). This initial screening research endoscopy is needed as current clinical care is variable (due to lack of guidelines for mapping and surveillance). The investigators anticipate enrolling 60 participants in the observational cohort for intensive gastric mapping, and then of these 60 participants, 32 eligible participants (after determining eligibility based on presence of high-risk features of the gastric intestinal metaplasia with confirmed extensive gastric intestinal metaplasia) will be included in the randomized control trial to receive either Pyrvinium (n=16) or placebo (n=16).

Treatment is planned as followed:

2 weeks of Pyrvinium vs placebo (within 3 months of initial research endoscopy).

Following the initial endoscopy, participants will receive placebo or Pyrvinium (2 mg/kg/day) by mouth once each day for a total of 14 days. The drug (or placebo) will be verified and dispensed from the investigational drug pharmacy using an IND with attention to safety and blinding to research participants and clinical research staff. The drug and placebo will be administered as liquid suspensions. Medication diary logs will be used and participants will be asked to return bottles that contained the medication.

All participants will be advised to use sunblock and wear protective clothing due to potential for sun-sensitivity.

Inclusion Criteria:

• Adults (including men, women, and non-binary individuals) over age 18 with known GIM with at least one high-risk feature (extensive vs limited, incomplete or mixed-type GIM, family history of stomach cancer),
• Ability to provide informed consent,
• Evidence of prior but not active H. pylori infection

Exclusion Criteria:

• Active gastric cancer diagnosis,
• High-risk of bleeding complications due to anticoagulants or underlying medical condition,
• Pregnancy (which is a contraindication to non-emergent endoscopy due to anesthesia risks)