Clinical Research Directory

Assessing Changes in Gadoxetate Metabolism by the Liver Using MRI

Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Summary

Identifying drugs at risk of interacting with other drugs, called drug-drug interaction (DDI), early in their development is crucial in avoiding late-stage drug development failures. The liver plays a key role in DDIs , with liver cells playing a major part in the taking up and getting rid of drugs. Currently, there is a lack of safe, widely available tools for testing DDIs in humans, particularly interactions involving liver cell transporters. This study is part of five work packages under the TRISTAN project (Translational Imaging in Drug Safety Assessment) which aims to improve drug safety using imaging. A pilot study provided proof-of-principle that the imaging procedure, dynamic gadoxetate (a type of dye) enhanced magnetic resonance imaging (DGE-MRI), can be used to measure the effect drugs have on the liver cell transporters in humans, using Rifampicin as a test drug. This study aims to further confirm DGE-MRI as a liver imaging biomarker in humans using two different drugs known to act on these transporters. All study procedures will be done at Sheffield Teaching Hospitals NHS Foundation Trust at the Royal Hallamshire Hospital. This is the site for University of Sheffield MRI related research. Healthy volunteer participants over the age of 18 years old will be eligible with the aim to recruit 12 volunteers. Each participant will attend 3 visits undertaken in a stepwise manner. Visit A will be for screening, consent and baseline blood tests. Visit B will include two MRI scans with gadoxetate administered at each and blood tests measuring liver function taken prior to each scan. Participants will proceed to Visit C if satisfactory images are obtained during the previous visit. Visit C will mirror Visit B, however either Metformin of Ciclosporin will be administered prior to the first scan. The study duration is three months.

Official title: Quantifying the Perturbation of Gadoxetate Kinetics by Metformin and Ciclosporin With Functional Magnetic Resonance Imaging of the Liver

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