Predicting Response and Exposure Changes in Cirrhosis for Effectiveness | NCT07750587

NCT07750587

Overview

NCT ID: NCT07750587
Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)OTHER
Official Title: Predicting Response and Exposure Changes in Cirrhosis for Effectiveness
Brief Summary: The goal of this clinical trial is to learn how liver cirrhosis affects the way the body processes drugs in adults with different stages of liver cirrhosis. This information may help improve drug dosing for people with liver cirrhosis in the future. The main question it aims to answer is:

• How does the severity of liver cirrhosis affect the way the body processes a combination of five drugs, each used to measure the activity of a different liver enzyme?

Researchers will compare participants with mild, moderate, and severe liver cirrhosis to see whether the processing of drugs differs between these groups.

Participants will:

Fast overnight for 8 hours before receiving the drugs

Have a scan to measure the stiffness of their liver and spleen

Receive a single low dose of five drugs: caffeine, warfarin, esomeprazole, metoprolol, and midazolam

Have blood samples taken before and at several times up to 72 hours after receiving the drugs, including samples for genetic testing and blood clotting checks

Avoid caffeine-containing food and drinks from 48 hours before receiving the drugs until the final blood sample

Status and Timeline

Status: Not yet recruiting
Last Update Posted: Aug 6, 2026Actual
Start Date: Nov 1, 2026Estimated
Primary Completion Date: Nov 1, 2028Estimated

Participation Criteria

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers?: No
Eligibility Criteria: Inclusion Criteria:

Age ≥ 18 years

Clinical, radiological and/or histological diagnosis of cirrhosis

Informed consent signed prior to participation in the study

Exclusion Criteria:

Original MELD score > 30

Estimated creatinine clearance < 30 mL/min, calculated by using the Cockcroft-Gault equation

Known poor metaboliser status for one of the CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A) described in the medical record

Previous clinically relevant adverse reaction or intolerance to one of the drugs in the probe drug cocktail

Recent exposure to one of the drugs in the drug probe cocktail within five elimination half-lives prior to drug administration (corresponding to approximately 1-10 days depending on the probe drug)36-40:

caffeine: 5h x 5 = 25 hours

warfarin: 50h x 5 = 250 hours

esomeprazole: 1.3h x 5 = 6.5 hours

metoprolol: 3.5h x 5 = 17.5 hours

midazolam: 2.5h x 5 = 12.5 hours

Absolute contraindication for one of the drugs in the probe drug cocktail36-40:

caffeine: drug hypersensitivity

warfarin: drug hypersensitivity and active bleeding

esomeprazole: drug hypersensitivity, congenital long QT syndrome and suspected gastrointestinal malignancy

metoprolol: drug hypersensitivity, cardiogenic shock, second- and third degree AV block, bradycardia (< 50 beats per minute), sick sinus syndrome including SA block, symptomatic hypotension (mean arterial pressure < 65 mmHg), metabolic acidosis and untreated pheochromocytoma

midazolam: drug hypersensitivity, severe chronic obstructive pulmonary disease, myasthenia gravis, sleep apnoea syndrome requiring CPAP, Parkinson's disease, severe respiratory insufficiency or acute respiratory depression

Interactions with strong to moderate CYP inhibitors and inducers of the following P450 enzymes: CYP1A2 (inhibitors: ciprofloxacin, fluvoxamine), CYP2C9, CYP2C19, CYP2D6 (inhibitors: bupropion, cinacalcet, fluoxetine, quinidine, paroxetine, terbinafine) and CYP3A (inducers: apalutamide, carbamazepine, efavirenz, enzalutamide, phenobarbital, phenytoin, hypericum, lumacaftor, mitotane, nevirapine, primidone, rifabutin, rifampicin; inhibitors: clarithromycin, cobicistat, erythromycin, itraconazole, ketoconazole, posaconazole, ritonavir, voriconazole)41,42

Use of concomitant medication with a clinically relevant PK or PD interaction with one or more components of the probe drug cocktail, if the interaction is expected to affect PK endpoint interpretation or compromise participant safety and cannot be appropriately managed

Refusing or unable to give informed consent (e.g. hepatic encephalopathy)

Study Plan

Study Type: Interventional
Phase: Not Applicable
Enrollment: 45Estimated
Primary Purpose: Other
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

Contacts and Locations

Central Contacts: Marten A Lantinga, MD PhDContact
m.a.lantinga@amsterdamumc.nl

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