GCC Agonist Signal in the Small Intestine

PRIMARY OBJECTIVE: I. To assess and compare participants randomly assigned 1:1:1 to one of three intervention arms (plecanatide 3 mg versus linaclotide 145 mcg versus no active agent) with respect to change in cyclic guanosine monophosphate (cGMP) accumulation in normal appearing duodenal mucosa specimens. SECONDARY OBJECTIVES: I. Characterization and comparison of the following outcomes (in prioritized order): Ia. cGMP levels in luminal fluid from participants receiving either linaclotide or plecanatide to fluid from participants receiving no agent; Ib. Vasodilator stimulated phosphoprotein (VASP) phosphorylation in normal-appearing duodenal mucosa biopsy specimens from participants receiving either linaclotide or plecanatide to those specimens from participants receiving no agent. EXPLORATORY OBJECTIVES: I. Comparison of cGMP and VASP phosphorylation between the plecanatide and linaclotide arms. II. Transcriptome analysis of cellular response (ribonucleic acid \[RNA\] sequencing analyses) to define whether GCC ligand exposure induces reproducible changes in duodenal messenger \[m\]RNA expression that can serve as a reliable biomarker of GCC-cGMP signaling in future studies. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive a single dose of plecanatide (3 mg) orally (PO) 60-120 minutes prior to standard of care esophagogastroduodenoscopy (EGD) with biopsy and luminal fluid collection. Patients also undergo biopsy on study. ARM II: Patients receive a single dose of linaclotide (145 mcg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection. Patients also undergo biopsy on study. ARM III: Patients undergo standard of care EGD with biopsy and luminal fluid collection. Patients also undergo biopsy on study. After completion of study intervention, patients are followed up at day 7.