GCC Agonist Signal in the Small Intestine

NCT ID: NCT05107219

Last Updated: 2025-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-30

Study Completion Date

2026-02-28

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Barrett Esophagus Gastroesophageal Reflux Disease Malignant Digestive System Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Arm I (plecanatide, EGD)

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.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of luminal fluid

Esophagogastroduodenoscopy

Intervention Type PROCEDURE

Undergo EGD

Plecanatide

Intervention Type DRUG

Given PO

Arm II (linaclotide, EGD)

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.

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of luminal fluid

Esophagogastroduodenoscopy

Intervention Type PROCEDURE

Undergo EGD

Linaclotide

Intervention Type DRUG

Given PO

Arm III (EGD)

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

Group Type ACTIVE_COMPARATOR

Biopsy

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of luminal fluid

Esophagogastroduodenoscopy

Intervention Type PROCEDURE

Undergo EGD

Interventions

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Biopsy

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo collection of luminal fluid

Intervention Type PROCEDURE

Esophagogastroduodenoscopy

Undergo EGD

Intervention Type PROCEDURE

Linaclotide

Given PO

Intervention Type DRUG

Plecanatide

Given PO

Intervention Type DRUG

Other Intervention Names

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BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection EGD [9-L-tyrosine]heat-stable enterotoxin (Escherichia coli)-(6-19)-peptide Linzess MD-1100 Trulance

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David S Weinberg

Role: PRINCIPAL_INVESTIGATOR

Fox Chase Cancer Center

Locations

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Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2021-11620

Identifier Type: REGISTRY

Identifier Source: secondary_id

UWI21-06-01

Identifier Type: OTHER

Identifier Source: secondary_id

UWI21-06-01

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA014520

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UG1CA242635

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2021-11620

Identifier Type: -

Identifier Source: org_study_id