NCT01950403

Phase I, Randomized, Placebo-Controlled Trial of Linaclotide to Demonstrate Colorectal Bioactivity in Healthy Volunteers

Completed Phase 1 Last updated 4 December 2024

What this trial tests

Phase 1 trial testing linaclotide acetate in Colorectal Cancer in 24 participants. Completed in 22 February 2018.

Timeline

1 September 2013

Primary endpoint
28 April 2016

22 February 2018

Quick facts

Lead sponsor	Mayo Clinic
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	basic science
Enrollment	24
Start date	1 September 2013
Primary completion	28 April 2016
Estimated completion	22 February 2018
Sites	1 location across United States

Drugs / interventions tested

• linaclotide acetate — full drug profile →
• placebo
• pharmacological study — full drug profile →
• laboratory biomarker analysis — full drug profile →

Conditions studied

• Colorectal Cancer — all drugs for Colorectal Cancer →
• Healthy, no Evidence of Disease — all drugs for Healthy, no Evidence of Disease →

Sponsor

Mayo Clinic

Who can join

Adults 18 to 65, any sex, with Colorectal Cancer or Healthy, no Evidence of Disease. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Dose of linaclotide acetate that produces a 60% response rate for cGMP levels in rectal tissue by radioimmunoassay (RIA)
  Time frame: Baseline to 7 days
  The pharmacological effect is measured by the arithmetic difference in mean cGMP levels before and after 7 days of linaclotide acetate in biopsies from the colonoscopy. The mean cGMP value will be calculated based on 2 biopsies from the rectum assessed at each time point. The PD response is measured by the difference in mean cGMP levels after 7 days.

Sponsor's own description

This randomized phase I trial studies the side effects and best dose of linaclotide acetate in preventing colorectal cancer in healthy volunteers. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of linaclotide acetate may prevent colorectal cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The paracrine hormone for the GUCY2C tumor suppressor, guanylin, is universally lost in colorectal cancer.
   Wilson C, Lin JE, Li P, Snook AE, et al · · 2014 · cited 50× · PMID 25304930 · DOI 10.1158/1055-9965.epi-14-0440
2. Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.
   Lin JE, Colon-Gonzalez F, Blomain E, Kim GW, et al · · 2016 · cited 48× · PMID 26773096 · DOI 10.1158/0008-5472.can-15-1467-t
3. Colorectal cancer: Genetic alterations, novel biomarkers, current therapeutic strategies and clinical trials.
   Housini M, Dariya B, Ahmed N, Stevens A, et al · · 2024 · cited 40× · PMID 37783294 · DOI 10.1016/j.gene.2023.147857
4. Bioactivity of Oral Linaclotide in Human Colorectum for Cancer Chemoprevention.
   Weinberg DS, Lin JE, Foster NR, Della'Zanna G, et al · · 2017 · cited 35× · PMID 28396341 · DOI 10.1158/1940-6207.capr-16-0286
5. Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer.
   Aka AA, Rappaport JA, Pattison AM, Sato T, et al · · 2017 · cited 26× · PMID 28162021 · DOI 10.1080/17512433.2017.1292124
6. GUCY2C ligand replacement to prevent colorectal cancer.
   Blomain ES, Pattison AM, Waldman SA. · · 2016 · cited 13× · PMID 27104761 · DOI 10.1080/15384047.2016.1178429
7. Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer.
   Blomain ES, Merlino DJ, Pattison AM, Snook AE, et al · · 2016 · cited 9× · PMID 27251363 · DOI 10.1124/mol.115.103192
8. Does obesity promote the development of colorectal cancer?
   Blomain ES, Waldman SA. · · 2016 · cited 8× · PMID 26943700 · DOI 10.1586/14737140.2016.1162102