In Vivo Predictive Dissolution 1

Healthy Clinical Trial

— iPD1  

Official title:

Development of MRI Protocols to Assess Gastrointestinal Motility With Concomitant Perfused Manometry Validation in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03191045
• Other study ID #: A14112016 MRI FDA
• Status: Completed
• Start date: July 19, 2017
• Est. completion date: March 1, 2018

Study information

• Verified date: January 2019
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 1, 2018
• Est. primary completion date: March 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Diagnostic Test:
• MRI and concomitant perfused manometry of bowel motility
We will carry out serial cine MRI of the bowel. At the same time we will record perfused manometry readings of the bowel in healthy adult participants.

Locations

Country	Name	City	State
United Kingdom	Nottingham Digestive Diseases Centre	Nottingham

Sponsors (3)

Lead Sponsor	Collaborator
University of Nottingham	Food and Drug Administration (FDA), University of Michigan

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stomach MRI and perfused manometry correlation	Correlation between the area under the curves (AUCs) of the MRI and perfused manometry stomach motility contractions	Over set time bins and recorded for up to 4 hours
Other	Small bowel MRI motility	Small bowel motility by MRI (both in arbitrary units and, where possible, using actual diameter readings as above in mm×second)	Over set time bins and recorded for up to 4 hours
Other	Small bowel perfused manometry motility	Small bowel motility by perfused manometry (as above, in mmHg×second)	Over set time bins and recorded for up to 4 hours
Other	Small bowel MRI and perfused manometry correlation	Correlation between the area under the curves (AUCs) of the MRI and perfused manometry small bowel motility contractions	Over set time bins and recorded for up to 4 hours
Other	Bowel liquid volumes	Gastric, small bowel water and colonic freely mobile liquid volumes (in mL)	Recorded for up to 4 hours
Primary	Stomach MRI motility	Area under the curve (AUC) of the stomach motility contractions (in mm×second) measured by MRI.	Over set time bins and recorded for up to 4 hours
Secondary	Stomach perfused manometry motility	Area under the curve (AUC) of the stomach motility contractions (in mmHg×second) measured by perfused manometry	Over set time bins and recorded for up to 4 hours