Mode of Action of Ondansetron, a 5-HT Receptor 3 Antagonist, in Lactulose Induced Diarrhoea

NCT03833999 | Completed Phase 4

• 1 other identifier: 85-1807
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blind, two period, two treatment crossover trial of ondansetron verses placebo studying the effects of ondansetron in the small and large bowel, specifically its effects on the amount of water in the gut, measured by MRI.

Conditions

Motility Disorder of Intestine; Ondansetron; Small Bowel Water

Keywords

ondansetron; small bowel water

Outcome Measures

Primary Outcomes (1)

• small bowel water content

  Change from baseline in area under the curve (AUC) small bowel water content

  0-6 hours post meal

Secondary Outcomes (3)

• small bowel motility (global motility score, arbitrary units)

  2 and 4 hours postprandially

• Weighted average position score (WAPS)

  baseline on day 3

• T1 of the ascending colon (T1AC)

  baseline on day 3

Study Arms (2)

Ondansetron and lactulose

EXPERIMENTAL

Ondansetron 8mg three times daily for 48 hours lactulose 20ml twice daily for 48 hours Serial abdominal MRI imaging

Drug: Ondansetron 8mg; Diagnostic Test: abdominal MRI; Drug: Lactulose

Placebo and lactulose

PLACEBO COMPARATOR

placebo oral capsule, one three times daily for 48 hours lactulose 20ml twice daily for 48 hours Serial abdominal MRI imaging

Diagnostic Test: abdominal MRI; Drug: Lactulose; Drug: Placebo oral capsule

Interventions

Ondansetron 8mg DRUG

ondansetron, a 5HT3 receptor antagonist used clinically in nausea and vomiting

Ondansetron and lactulose

abdominal MRI DIAGNOSTIC_TEST

serial MRIs on day 1 and day 3 of the study, at baseline and 2 hours apart 0-6 hours after meal ingestion on day 1 and 0-4 hours after the meal on day 3

Ondansetron and lactulose; Placebo and lactulose

Lactulose DRUG

Participants will receive 20mls lactulose twice daily for 48 hours prior to the third study day

Ondansetron and lactulose; Placebo and lactulose

Placebo oral capsule DRUG

overcoated placebo tablet, identical to the ondansetron

Placebo and lactulose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 18 or older
• able to give informed consent

You may not qualify if:

• Pregnancy declared by candidate
• History declared by the candidate of pre-existing gastrointestinal disorder that may affect bowel function, congenital long QT syndrome or QTc \>450msecs for males or 470 msecs for female on screening ECG.
• A positive diagnosis of irritable bowel syndrome based on the Rome IV criteria questionnaire
• Reported history of previous resection of the oesophagus, stomach or intestine (excluding appendix)
• Intestinal stoma
• Any medical condition making participation potentially compromising participation in the study e.g. diabetes mellitus, respiratory disease limiting ability to lie in the scanner, known allergy to one of the food products
• Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
• Will not agree to dietary restrictions required during the MRI study day
• Inability to lie flat or exceed scanner limits of weight \<120kg
• Poor understanding of English language
• Participation in night shift work the week prior to the study day. Night work is defined as working between midnight and 6.00 AM
• Participation in any medical trials for the past 3 months
• Anyone who in the opinion of the investigator is unlikely to be able to comply with the protocol e.g. cognitive dysfunction, chaotic lifestyle related to substance abuse

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

University of Nottingham

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

MeSH Terms

Interventions

Ondansetron; Lactulose

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Robin Spiller

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double-blind, two-period, two-treatment crossover trial

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: February 7, 2019
• Study Start: October 16, 2018
• Primary Completion: June 27, 2019
• Study Completion: June 27, 2019
• Last Updated: November 27, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)