GCC Agonist Signal in the Small Intestine
Primary Purpose
Barrett Esophagus, Gastroesophageal Reflux Disease, Malignant Digestive System Neoplasm
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Biopsy
Biospecimen Collection
Esophagogastroduodenoscopy
Linaclotide
Plecanatide
Sponsored by
About this trial
This is an interventional prevention trial for Barrett Esophagus
Eligibility Criteria
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 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 =< 1
- Not pregnant or breastfeeding, as determined by clinical administration of 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 childbearing 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
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 including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- History of gastric bypass, gastric sleeve, or bariatric surgery
Sites / Locations
- Mayo Clinic in Arizona
- Thomas Jefferson University HospitalRecruiting
- Fox Chase Cancer CenterRecruiting
- University of Wisconsin Carbone Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Arm I (plecanatide, EGD)
Arm II (linaclotide, EGD)
Arm III (EGD)
Arm Description
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.
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 undergo standard of care EGD with biopsy and luminal fluid collection.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
cGMP levels in luminal fluid
Vasodilator-stimulated phosphoprotein (VASP) phosphorylation in normal appearing duodenal mucosa
Full Information
NCT ID
NCT05107219
First Posted
November 3, 2021
Last Updated
October 12, 2023
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT05107219
Brief Title
GCC Agonist Signal in the Small Intestine
Official Title
Pilot Study of GCC Agonists to Identify a Cyclic-GMP Signal in Duodenal Tissue of Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 25, 2022 (Actual)
Primary Completion Date
February 1, 2025 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Barrett Esophagus, Gastroesophageal Reflux Disease, Malignant Digestive System Neoplasm
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
43 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm I (plecanatide, EGD)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II (linaclotide, EGD)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm III (EGD)
Arm Type
Active Comparator
Arm Description
Patients undergo standard of care EGD with biopsy and luminal fluid collection.
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo biopsy
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of luminal fluid
Intervention Type
Procedure
Intervention Name(s)
Esophagogastroduodenoscopy
Other Intervention Name(s)
EGD
Intervention Description
Undergo EGD
Intervention Type
Drug
Intervention Name(s)
Linaclotide
Other Intervention Name(s)
[9-L-tyrosine]heat-stable enterotoxin (Escherichia coli)-(6-19)-peptide, Linzess, MD-1100
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Plecanatide
Other Intervention Name(s)
Trulance
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Cyclic guanosine monophosphate (cGMP) levels
Description
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.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
cGMP levels in luminal fluid
Time Frame
Up to 2 years
Title
Vasodilator-stimulated phosphoprotein (VASP) phosphorylation in normal appearing duodenal mucosa
Time Frame
Up to 2 years
Other Pre-specified Outcome Measures:
Title
Comparison pf cGMP and VASP phosphorylation between the plecanatide and linaclotide arms
Time Frame
Up to 2 years
Title
Cellular response
Description
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.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David S Weinberg
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Niloy J. Samadder
Phone
480-342-6263
Email
sammader.jewel@mayo.edu
First Name & Middle Initial & Last Name & Degree
Niloy J. Samadder
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Scott A. Waldman
Phone
215-955-6086
Email
Scott.waldman@jefferson.edu
First Name & Middle Initial & Last Name & Degree
Scott A. Waldman
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David S. Weinberg
Phone
215-444-1424
Email
David.Weinberg@fccc.edu
First Name & Middle Initial & Last Name & Degree
David S. Weinberg
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Howard H. Bailey
Phone
608-263-8624
Email
hhbailey@medicine.wisc.edu
First Name & Middle Initial & Last Name & Degree
Howard H. Bailey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm
Learn more about this trial
GCC Agonist Signal in the Small Intestine
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