In Vivo Predictive Dissolution 1

Completed

• Conditions: Healthy
• Interventions: Diagnostic Test: MRI and concomitant perfused manometry of bowel motility

• Registration Number: NCT03191045
• Lead Sponsor: University of Nottingham

Brief Summary

This study will: 1. validate MRI motility method with concomitant perfused manometry method in healthy adult participants. 2. measure exploratory endpoints of interest including GI fluid volumes in 21 adult healthy volunteers studied twice.

Detailed Description

The gastrointestinal (GI) environment where drug products dissolve has not been studied in detail due to limitations, especially invasiveness of existing techniques. Hence little in vivo data on GI fluids and motility is available to improve relevance of predictive dissolution models and bench dissolution techniques. Recent advances in magnetic resonance imaging (MRI) methods could provide novel data and insights. On-going studies at the University of Michigan and at the University of Nottingham, using advanced, validated, quantitative MRI techniques have already shown that GI fluid (water) volumes can be measured. The classical method for measuring GI motility is via a manometric method involving intubation, but it is possible to measure GI motility with MRI. Based on our MRI motility pilot data and on the literature available, this study aims to test the main hypotheses that in healthy adult participants the new MRI method has the potential to replace current manometric study protocols and will allow a simultaneous measurement of gastrointestinal motility and fluid volumes in the gut during the fasted state. This will establish a solid and unprecedented base of in vivo results upon which to base advances in oral pharmaceutical product science. For this initial study, the study objectives are therefore: 1. To validate the MRI motility method with concomitant perfused manometry method in healthy adult participants. 2. To measure exploratory endpoints of interest including GI fluid volumes. Twenty one adult healthy volunteers will participate in this replicated study. We will pass a thin perfused manometry tube via the nose into the gut of the participants and then take MRI images of abdominal areas while bowel motility is being measured via a tube manometric method to see how they compare. We will be able also to measure the volume of fluids in the gut.

Study Timeline

• Study First Submitted: 2017-06-15
• Study First Submitted QC: 2017-06-15
• Study First Posted: 2017-06-19
• Study Start: 2017-07-19
• Primary Completion: 2018-03-01
• Study Completion: 2018-03-01
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-15
• Last Update Posted: 2019-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Aged 18-60
• Healthy
• Male or female
• Able to give informed written consent and willing to comply with required study procedures

Exclusion Criteria

• Any history of serious, unstable medical condition, unstable/uncontrolled diabetes mellitus, and/ or major psychiatric diagnosis such as attention deficit hyperactivity disorder, obsessive compulsive disorder, panic attacks and generalized anxiety disorder.
• Any reported history of gastrointestinal disease
• Any significant respiratory disease such as asthma
• Any conditions requiring daily intake of any prescription and/or over-the-counter medications
• Any reported history of surgery that could affect gastrointestinal function (e.g. colectomy, small bowel resection)
• Reported alcohol dependence
• Abnormal screening procedures and laboratory results that are clinically significant in the opinion of the study medically qualified researcher
• Pregnancy
• Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
• Inability to lie flat
• Weight exceeding scanner limits of 120kg
• Poor understanding of English language
• Any conditions causing fidgeting
• Claustrophobia
• Participation of any medical trials for the past 3 months
• Judgement by the study medically qualified researcher that the candidate will be unable to comply with the full study protocol e.g. severe chronic obstructive pulmonary disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy participants	MRI and concomitant perfused manometry of bowel motility	A group of 21 healthy adult participants studied twice (test-retest)

Primary Outcome Measures

Name	Time	Method
Stomach MRI motility	Over set time bins and recorded for up to 4 hours	Area under the curve (AUC) of the stomach motility contractions (in mm×second) measured by MRI.

Secondary Outcome Measures

Name	Time	Method
Stomach perfused manometry motility	Over set time bins and recorded for up to 4 hours	Area under the curve (AUC) of the stomach motility contractions (in mmHg×second) measured by perfused manometry

Trial Locations

Locations (1)

Nottingham Digestive Diseases Centre; 🇬🇧 Nottingham, United Kingdom