Effect to Linaclotide on Colonic Motility

NCT ID: NCT06989268

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-10
• Study Completion Date: 2015-06-03

Brief Summary

This study aim was to evaluate the effect of Linaclotide, a pharmacological treatment normally used to treat functional constipation or irritable bowel syndrome with predominant constipation, on colonic motility as assessed by high-resolution colonic manometry.

Detailed Description

Rationale: Several treatments with different modes of action are currently available for chronic constipation, including the osmotic laxative polyethylene glycol (PEG), the stimulant laxative bisacodyl, the prokinetic prucalopride and the secretagogue linaclotide. In a previous study conducted in our lab (study S54750) it has been hypothesized that only bisacodyl and prucalopride activate colonic motility. However the results have demonstrated that PEG, bisacodyl and prucalopride did not differ in their effect on colonic motility index, except for bisacodyl which induced HAPCs in a greater number of healthy subjects as compared to both prucalopride and PEG. To our knowledge, the effect of linaclotide on colonic motility has never been studied in humans.

Objectives: Primary: to evaluate the effects of linaclotide as compared to placebo on motility index and on the number of colonic high amplitude propagated contractions (HAPCs) during a 8-hour intraluminal manometry in healthy subjects. Secondary: to evaluate the association between motility parameters and sensations (abdominal gas, desire to defecate, urgency to defecate and abdominal discomfort) as well as number and consistency of bowel movements.

Investigational product, dose, and mode of administration: Regimen A: 290 μg linaclotide once daily oral administration with 125mL of water. Regimen B: placebo, empty capsule, once daily oral administration with 125mL of water.

Methodology: This is randomized, placebo controlled, 2-period cross-over study investigating the effects of placebo and linaclotide on colon motility with intraluminal manometry. On each of Treatment Period, a manometry catheter will be placed in the colon under conscious sedation and the colonic pressure will be continuously measured through 8 hours after administration of each of the investigational products (Regimen A or B).

Inclusion criteria: healthy male and non-pregnant, non-breastfeeding female participants, aged 18-65 years old at the time of consent.

Exclusion criteria: use of medications within 48 h of dose initiation; structural or metabolic diseases that affect the gastrointestinal system and functional gastrointestinal disorders; previous abdominal surgery other than appendectomy, cholecystectomy, hysterectomy, or hernia repair; known illnesses such as diabetes, cardiovascular or lung disease; use of agents that influence bowel habit, i.e. anticholinergics (not including antihistamines with anticholinergic properties), spasmolytics and prokinetics in the 7 days before the study.

Conditions

Chronic Constipation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Linaclotide

290 μg linaclotide once daily oral administration with 125mL of water

Group Type: ACTIVE_COMPARATOR

Linaclotide 290 micrograms

Intervention Type: DRUG

290 μg linaclotide once daily oral administration with 125mL of water

Placebo

placebo, empty capsule, once daily oral administration with 125mL of water

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo, empty capsule, once daily oral administration with 125mL of water

Interventions

Linaclotide 290 micrograms

290 μg linaclotide once daily oral administration with 125mL of water

Intervention Type: DRUG

Placebo

Placebo, empty capsule, once daily oral administration with 125mL of water

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• healthy male and non-pregnant, non-breastfeeding female participants, aged 18-65 years old at the time of consent

Exclusion Criteria

• use of medications within 48 h of dose initiation; structural or metabolic diseases that affect the gastrointestinal system and functional gastrointestinal disorders; previous abdominal surgery other than appendectomy, cholecystectomy, hysterectomy, or hernia repair; known illnesses such as diabetes, cardiovascular or lung disease; use of agents that influence bowel habit, i.e. anticholinergics (not including antihistamines with anticholinergic properties), spasmolytics and prokinetics in the 7 days before the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Tack, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Other Identifiers

S56101

Identifier Type: -

Identifier Source: org_study_id