Assessing Changes in Gadoxetate Metabolism by the Liver Using MRI

NCT07541807 | Completed

• 2 other identifiers: STH23320116106
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Liver Dysfunction

Keywords

MRI; Gadoxetate; imaging biomarker; liver

Outcome Measures

Primary Outcomes (2)

• To evaluate the rate of gadoxetate uptake

  quantitative variables extracted from the MRI data. 95% CI on the mean effect size of uptake rate khe (mL/min/100mL)

  Visit B which is performed at baseline, Visit C which is performed within 56 days of baseline visit B

• To evaluate the rate of gadoxetate excretion

  quantitative variables extracted from the MRI data. 95% CI on the mean effect size of excretion rate kbh (mL/min/100mL

  Visit B which is performed at baseline, Visit C which is performed within 56 days of baseline visit B

Secondary Outcomes (8)

• Evaluate effect size of gadoxetate uptake rates as measured by DGE-MRI in response to test drug administration.

  Visit B which is performed at baseline, Visit C which is performed within 56 days of baseline visit B

• Evaluate effect size of gadoxetate clearance rates as measured by DGE-MRI in response to test drug administration.

  Visit B which is performed at baseline, Visit C which is performed within 56 days of baseline visit B

• Evaluate liver function test results in response to test drug administration.

  Visit B which is performed at baseline, Visit C which is performed within 56 days of baseline visit B

• Evaluate effect size of the drug on relative enhancement ratio of the liver

  Visit B which is performed at baseline, Visit C which is performed within 56 days of baseline visit B

• Evaluate effect size of the drug on area under the curve in blood concentrations.

  Visit B which is performed at baseline, Visit C which is performed within 56 days of baseline visit B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers responding to a call for study participation (online advertisements).

You may qualify if:

• Able to provide informed consent
• Age above 18 years
• Able to attend for all scheduled visits
• Able to adhere to instructions on pre-scan food and drinks intake
• Able to lie flat for the duration of the scan

You may not qualify if:

• No history of liver or kidney disease
• No history of heart failure
• No history of uncontrolled hypertension
• No history of malignancy or premalignant conditions, past or present
• No current uncontrolled infections
• Not currently pregnant
• Not currently breastfeeding
• No regular prescribed medication, except the oral contraceptive pill
• Cochlear implant
• Aneurysm clips
• Neurological stimulator
• Implanted cardiac devices (ICD, PPM, loop recorders, or any others)
• Metal heart valve
• History of retained metal foreign bodies
• Other implanted metal device which prevents MR imaging

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• University of Sheffield: collaborator

Study Sites (2)

University of Sheffield, POLARIS, 18 Claremont Crescent

Sheffield, S10 2RX, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, United Kingdom

Location

Related Publications (4)

• Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705. doi: 10.1111/j.1476-5381.2009.00430.x. Epub 2009 Sep 25.

  PMID: 19785645 BACKGROUND

• Melillo N, Scotcher D, Kenna JG, Green C, Hines CDG, Laitinen I, Hockings PD, Ogungbenro K, Gunwhy ER, Sourbron S, Waterton JC, Schuetz G, Galetin A. Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats. Pharmaceutics. 2023 Mar 10;15(3):896. doi: 10.3390/pharmaceutics15030896.

  PMID: 36986758 BACKGROUND

• Ruan G, Wu F, Shi D, Sun H, Wang F, Xu C. Metformin: update on mechanisms of action on liver diseases. Front Nutr. 2023 Dec 14;10:1327814. doi: 10.3389/fnut.2023.1327814. eCollection 2023.

  PMID: 38192642 BACKGROUND

• Gertz M, Cartwright CM, Hobbs MJ, Kenworthy KE, Rowland M, Houston JB, Galetin A. Cyclosporine inhibition of hepatic and intestinal CYP3A4, uptake and efflux transporters: application of PBPK modeling in the assessment of drug-drug interaction potential. Pharm Res. 2013 Mar;30(3):761-80. doi: 10.1007/s11095-012-0918-y. Epub 2012 Nov 22.

  PMID: 23179780 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples that will be destroyed at the end of the study.

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Benjamin Rea

  Sheffield Teaching Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2025
• First Posted: April 21, 2026
• Study Start: December 2, 2024
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: All data collated or generated during this research study will be stored short term on an encrypted shared Drive (administered by university IT) with only the investigators and research fellows having access. Upon completion of the research activities all data will be deleted from this short term storage and will be stored, fully anonymised, in a long-term repository. A digitally encrypted key file, linking Study ID to participant names, date of birth and contact details, will be stored on the local STH drives, separate from all other study data. The key file will be securely stored for 5 years at the end of the study, after all MRI scans on all participants have been completed. Upon completion of the study, imaging data will be fully anonymised and stored in the university-owned Google Drive. Anonymous data may be made publicly available on zenodo.org in the future, also serving as a long-term repository.
• Access Criteria: All data collated or generated during this research study will be stored short term on an encrypted shared Drive (administered by university IT) with only the investigators and research fellows having access. At the end of each scan, MRI data will be exported anonymously using the participant's Study ID. Anonymised MR images will be exported in DICOM (Digital Imaging and Communication) format to the shared encrypted research group University of Sheffield Google Drive for primary analysis. Data for primary analysis will be performed with in-house software on an encrypted University of Sheffield computer.

Locations

GB (2)