What is the mechanism of action of this treatment?

Linaclotide, a treatment for Colorectal Adenomas, functions by binding to receptors on intestinal cells, leading to increased secretion of water and salt into the intestinal lumen. This action helps to soften stools and promote bowel movements, which is crucial for patients suffering from constipation associated with Colorectal Adenomas. Effective management of bowel movements can significantly improve the quality of life for these patients by reducing symptoms such as abdominal pain, bloating, and straining. Other treatments may also target similar pathways to enhance intestinal fluid secretion and improve colonic motility.

What side effects are associated with this type of intervention?

Common treatments for colorectal adenomas that promote water and salt secretion in the intestines include linaclotide. The known side effects of linaclotide primarily involve gastrointestinal symptoms such as diarrhea, abdominal pain, and bloating. These side effects occur because linaclotide increases fluid secretion in the intestines, which can lead to loose stools and discomfort. Other potential side effects may include gas and a feeling of fullness or pressure in the abdomen.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of colorectal adenomas, though not all specifically target the same mechanism as linaclotide. Linaclotide, which promotes water and salt secretion in the intestines, is primarily used for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). For colorectal adenomas, treatments often focus on chemoprevention and include drugs like celecoxib, a COX-2 inhibitor, which has been approved for reducing the number of adenomatous colorectal polyps in patients with familial adenomatous polyposis (FAP). While not directly similar to linaclotide, these treatments aim to manage or reduce the risk of adenoma formation through different mechanisms.

What other types of research exist?

Promising novel alternatives to Linaclotide for colorectal adenomas include somatostatin analogs like octreotide and lanreotide, which have shown antiproliferative effects in neuroendocrine tumors and may have potential in colorectal adenomas. Additionally, everolimus, an mTOR inhibitor, has demonstrated efficacy in various gastrointestinal tumors and could be considered for colorectal adenomas.

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Guanylate Cyclase-C Agonist

Linaclotide for Colorectal Cancer

Phase 2

Waitlist Available

Led By Scott Waldman, MD

Research Sponsored by Sidney Kimmel Cancer Center at Thomas Jefferson University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

History of 1 or more sporadic colorectal adenoma on previous endoscopy (adenoma cohort) or stage 0-3 biopsy proven colorectal cancer (CRC) (colorectal cancer cohort) who are scheduled for a surgical procedure

Be older than 18 years old

Must not have

Has taken linaclotide within 30 days prior to consent

At risk for obstructing or near-obstructing mechanical gastrointestinal obstruction

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Summary

This trial studies how well linaclotide works in patients with early-stage colorectal cancer. Linaclotide helps the intestines release water and salt by binding to cell receptors. Researchers want to see if it affects cancer-related markers. Linaclotide is an FDA-approved drug primarily used for treating chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C).

Who is the study for?

This trial is for individuals with stages 0-3 colorectal cancer or those who've had colorectal adenomas. Participants must be able to swallow capsules, sign consent forms, maintain pill diaries, and use effective contraception if of childbearing potential. Exclusions include certain digestive diseases, recent linaclotide use, other cancers treated within the last 6 months (except some skin cancers), current participation in other trials or severe health issues.

What is being tested?

The study is testing how well linaclotide works for patients with early-stage colorectal cancer by comparing it to a placebo. Linaclotide is a small protein that encourages intestinal cells to release water and salt. The trial will see if this treatment can benefit patients awaiting surgery.

What are the potential side effects?

Linaclotide may cause side effects such as diarrhea due to increased intestinal secretion of water and salt. It might also lead to abdominal pain, bloating, gas, or an urgent need to go to the bathroom.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had at least one non-hereditary colorectal adenoma or I have stage 0-3 colorectal cancer and am scheduled for surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have taken linaclotide in the last 30 days.

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I am at risk for a severe blockage in my digestive tract.

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I do not have any uncontrolled illnesses that could affect my study participation.

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I have a history of delayed stomach emptying.

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I have inflammatory bowel disease (Crohn's or ulcerative colitis).

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I have been diagnosed with a type of colitis.

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I have been diagnosed with celiac disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Pharmacodynamics effect on cGMP levels

Secondary study objectives

GUCY2C expression

Guanylin levels

Incidence of adverse events (AEs)

+1 more

Other study objectives

Axin and c-Myc messenger ribonucleic acid (mRNA) levels

Beta-catenin levels

Beta-catenin nuclear localization

+2 more

Side effects data

From 2018 Phase 4 trial • 828 Patients • NCT02590432

26%

Diarrhoea

Flatulence

100%

80%

60%

40%

20%

Study treatment Arm

LINZESS® 145 μg (CIC)

LINZESS® 290 μg (IBS-C)

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Arm I (linaclotide)Experimental Treatment1 Intervention

Patients receive linaclotide PO daily on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.

Group II: Arm II (placebo)Placebo Group1 Intervention

Patients receive placebo PO QD on days 1-7 and undergo standard of care colonoscopy or surgery on day 7.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Linaclotide

2008

Completed Phase 4

~9200

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Linaclotide, a treatment for Colorectal Adenomas, functions by binding to receptors on intestinal cells, leading to increased secretion of water and salt into the intestinal lumen. This action helps to soften stools and promote bowel movements, which is crucial for patients suffering from constipation associated with Colorectal Adenomas. Effective management of bowel movements can significantly improve the quality of life for these patients by reducing symptoms such as abdominal pain, bloating, and straining. Other treatments may also target similar pathways to enhance intestinal fluid secretion and improve colonic motility.

Cyclic nucleotide concentrations in 1,2-dimethylhydrazine induced rat colon adenocarcinoma.Laxative Effects of Yangyin Tongmi Capsule on a Model of Diphenoxylate-Induced Constipation in Mice.Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability.