GCC Agonist Signal in the Small Intestine

NCT05107219 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: NCI-2021-11620UWI21-06-01P30CA014520UG1CA242635
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

Brief Summary

This early phase I trial studies the guanylyl cyclase C (GCC) agonist effect on cGMP signal in duodenal tissue. Plecanatide and linaclotide are drugs approved by the Food and Drug Administration for the treatment of conditions related to constipation. This trial aims to see the effects of taking either one of two drugs, plecanatide or linaclotide, or no drug, on a certain chemical found in the tissue collected from small intestine and how they compare.

Conditions

Barrett Esophagus; Gastroesophageal Reflux Disease; Malignant Digestive System Neoplasm

Outcome Measures

Primary Outcomes (1)

• Cyclic guanosine monophosphate (cGMP) levels

  Will compare cGMP levels measured in normal-appearing duodenal mucosa biopsy specimens from participants receiving linaclotide or plecanatide to cGMP levels in specimens from participants receiving no active treatment. Will evaluate the difference between the control and each treated arm in cGMP levels using two-tailed two-sample Student t-tests. If necessary, a log transformation or Wilcoxon rank-sum will be used, as appropriate.

  Up to 2 years

Secondary Outcomes (2)

• cGMP levels in luminal fluid

  Up to 2 years

• Vasodilator-stimulated phosphoprotein (VASP) phosphorylation in normal appearing duodenal mucosa

  Up to 2 years

Other Outcomes (2)

• Comparison pf cGMP and VASP phosphorylation between the plecanatide and linaclotide arms

  Up to 2 years

• Cellular response

  Up to 2 years

Study Arms (3)

Arm I (plecanatide, EGD)

EXPERIMENTAL

Patients receive a single dose of plecanatide (3 mg) PO 60-120 minutes prior to standard of care EGD with biopsy and luminal fluid collection.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Esophagogastroduodenoscopy; Drug: Plecanatide

Arm II (linaclotide, EGD)

EXPERIMENTAL

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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Esophagogastroduodenoscopy; Drug: Linaclotide

Arm III (EGD)

ACTIVE COMPARATOR

Patients undergo standard of care EGD with biopsy and luminal fluid collection.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Esophagogastroduodenoscopy

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Arm I (plecanatide, EGD); Arm II (linaclotide, EGD); Arm III (EGD)

Biospecimen Collection PROCEDURE

Undergo collection of luminal fluid

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (plecanatide, EGD); Arm II (linaclotide, EGD); Arm III (EGD)

Esophagogastroduodenoscopy PROCEDURE

Undergo EGD

Also known as: EGD

Arm I (plecanatide, EGD); Arm II (linaclotide, EGD); Arm III (EGD)

Linaclotide DRUG

Given PO

Also known as: [9-L-tyrosine]heat-stable enterotoxin (Escherichia coli)-(6-19)-peptide, Linzess, MD-1100

Arm II (linaclotide, EGD)

Plecanatide DRUG

Given PO

Also known as: Trulance

Arm I (plecanatide, EGD)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Scheduled for clinically indicated esophagogastroduodenoscopy (EGD)
• Age \>= 18 years of age. Note: Because no dosing or adverse event (AE) data are currently available on the use of plecanatide or linaclotide in participants \< 18 years of age, children and adolescents are excluded from this study but will be eligible for future pediatric trials, if applicable
• Willing to provide mandatory biospecimens as specified in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Not pregnant or breastfeeding, as determined by pregnancy test prior to EGD procedure. Note: The effects of plecanatide and linaclotide on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 2 weeks after discontinuing study agent. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. Breastfeeding should be discontinued if the mother is treated with plecanatide or linaclotide
• Ability to understand and the willingness to sign a written informed consent document
• 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
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible

You may not qualify if:

• Prior treatment in the past week with plecanatide, linaclotide, or other agent whose primary mechanism of action is that of a GCC agonist
• History of allergic reactions attributed to compounds of similar chemical or biologic composition of plecanatide or linaclotide
• Use of any other investigational agents =\< 12 weeks prior to registration
• Uncontrolled intercurrent illness, or psychiatric illness/social situations that would limit compliance with study requirements
• History of gastric bypass, gastric sleeve, or bariatric surgery

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Barrett Esophagus; Gastroesophageal Reflux; Gastrointestinal Neoplasms

Interventions

Biopsy; Specimen Handling; Endoscopy, Digestive System; linaclotide; plecanatide

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Esophageal Motility Disorders; Deglutition Disorders; Digestive System Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Diagnostic Techniques, Digestive System; Endoscopy; Digestive System Surgical Procedures; Minimally Invasive Surgical Procedures

Study Officials

• David S Weinberg

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: November 4, 2021
• Study Start: November 30, 2022
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: December 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (4)