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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05107219
Other study ID # NCI-2021-11620
Secondary ID NCI-2021-11620UW
Status Recruiting
Phase Phase 1
First received
Last updated
Start date November 30, 2022
Est. completion date February 1, 2025

Study information

Verified date April 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 43
Est. completion date February 1, 2025
Est. primary completion date February 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Procedure:
Biopsy
Undergo biopsy
Biospecimen Collection
Undergo collection of luminal fluid
Esophagogastroduodenoscopy
Undergo EGD
Drug:
Linaclotide
Given PO
Plecanatide
Given PO

Locations

Country Name City State
United States University of Wisconsin Carbone Cancer Center - University Hospital Madison Wisconsin
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States Thomas Jefferson University Hospital Philadelphia Pennsylvania
United States Mayo Clinic in Arizona Scottsdale Arizona

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Comparison pf cGMP and VASP phosphorylation between the plecanatide and linaclotide arms Up to 2 years
Other Cellular response Transcriptome analysis of cellular response (ribonucleic acid [RNA] sequencing analyses), to define whether guanylyl cyclase C (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. Up to 2 years
Primary 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 cGMP levels in luminal fluid Up to 2 years
Secondary Vasodilator-stimulated phosphoprotein (VASP) phosphorylation in normal appearing duodenal mucosa Up to 2 years
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