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| Name | Class |
|---|---|
| Food and Drug Administration (FDA) | FED |
| University of Michigan | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy participants | A group of 21 healthy adult participants studied twice (test-retest) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MRI and concomitant perfused manometry of bowel motility | Diagnostic Test | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Small bowel MRI motility |
Inclusion Criteria:
Exclusion Criteria:
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Self-reporting, healthy adult participants, with no restrictions on gender, ethnicity or race, recruited by advertisement by poster and flyer
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| Name | Affiliation | Role |
|---|---|---|
| Luca Marciani, PhD | University of Nottingham | Principal Investigator |
| Gordon L Amidon, PhD | University of Michigan | Principal Investigator |
| Greg E Amidon, PhD | University of Michigan | Principal Investigator |
| Maura Corsetti, MD | University of Nottingham | Principal Investigator |
| Jeff Wright, PhD | University of Nottingham | Principal Investigator |
| Paul Glover, PhD | University of Nottingham | Principal Investigator |
| Geoffrey S Hebbard, PhD | Melbourne Health | Principal Investigator |
| Caroline L Hoad, PhD | University of Nottingham | Principal Investigator |
| Penny A Gowland, PhD | University of Nottingham | Principal Investigator |
| Kerby Shedden, PhD |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nottingham Digestive Diseases Centre | Nottingham | Ng7 2UH | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33175860 | Derived | 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. |
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| ID | Term |
|---|---|
| D008279 | Magnetic Resonance Imaging |
| ID | Term |
|---|---|
| D014054 | Tomography |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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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 |
| 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 |
| 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 |
| Bowel liquid volumes | Gastric, small bowel water and colonic freely mobile liquid volumes (in mL) | Recorded for up to 4 hours |
| University of Michigan |
| Principal Investigator |
| Joseph Dickens, PhD | University of Michigan | Principal Investigator |
| Robin C Spiller, MD | University of Nottingham | Principal Investigator |