Clinical trial NCT03191045: In Vivo Predictive Dissolution 1
Official title: Development of MRI Protocols to Assess Gastrointestinal Motility With Concomitant Perfused Manometry Validation in Healthy Volunteers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy
Keywords: MRI
motility
perfused manometry
stomach
bowel
water
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
name: University of Michigan
First posted: 2017-06-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Self-reporting, healthy adult participants, with no restrictions on gender, ethnicity or race, recruited by advertisement by poster and flyer

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.

Eligibility criteria: 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

Primary outcomes:
measure: Stomach MRI motility
timeFrame: Over set time bins and recorded for up to 4 hours
Secondary outcomes:
measure: Stomach perfused manometry motility
timeFrame: Over set time bins and recorded for up to 4 hours
Other outcomes:
measure: Stomach MRI and perfused manometry correlation
timeFrame: Over set time bins and recorded for up to 4 hours
measure: Small bowel MRI motility
timeFrame: Over set time bins and recorded for up to 4 hours
measure: Small bowel perfused manometry motility
timeFrame: Over set time bins and recorded for up to 4 hours
measure: Small bowel MRI and perfused manometry correlation
timeFrame: Over set time bins and recorded for up to 4 hours
measure: Bowel liquid volumes
timeFrame: Recorded for up to 4 hours
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham Digestive Diseases Centre
Study officials:
affiliation: University of Nottingham
name: Luca Marciani, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Gordon L Amidon, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Greg E Amidon, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Maura Corsetti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Jeff Wright, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Paul Glover, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Melbourne Health
name: Geoffrey S Hebbard, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Caroline L Hoad, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Penny A Gowland, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Kerby Shedden, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Joseph Dickens, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Robin C Spiller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heissam K, Abrehart N, Hoad CL, Wright J, Menys A, Murray K, Glover PM, Hebbard G, Gowland PA, Baker J, Hasler WL, Spiller RC, Corsetti M, Brasseur JG, Hens B, Shedden K, Dickens J, Mudie DM, Amidon GE, Amidon GL, Marciani L. Measurement of fasted state gastric antral motility before and after a standard bioavailability and bioequivalence 240 mL drink of water: Validation of MRI method against concomitant perfused manometry in healthy participants. PLoS One. 2020 Nov 11;15(11):e0241441. doi: 10.1371/journal.pone.0241441. eCollection 2020.