Cells of Monocytic Origin as Surrogate Markers for Individual Drug Effects and Hepatotoxicity

November 23, 2019 updated by: Andreas Benesic, MD
Drug metabolism in the liver is subject to large fluctuations (differences between women and men, people of different ethnic backgrounds, children and adults). These large differences are responsible for very different drug effects and side-effects (and especially liver damage caused by drugs) between individuals. Recent scientific findings suggest that blood derived cells can be used to model individual effects of drugs on the liver reflect inter-individual differences. Since liver damage caused by drugs is a diagnosis of exclusion, the aforementioned cells can be used to identify patients that show higher sensitivity to hepatotoxic side-effects and - in case several drugs are involved - identify the causal agent or possible interactions.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Drug-induced liver injury (DILI), especially its idiosyncratic for is often an unpredictable complication of drug therapy. Until now it is very challenging to predict occurrence, severity and outcome of DILI. Previous data provide evidence that cells from peripheral blood may reflect hepatocellular damage (Fannin RD, Hepatology. 2010). Own research could show that peripheral monocytes are capable to obtain several hepatocyte-like functions while maintaining individual characteristics of the donor, especially cytochrome P450 metabolism (Benesic, Gerbes, et al, Lab Invest 2012). This study investigates the effects of potentially hepatotoxic drugs on cells generated from patient blood in comparison to the clinical presentation. Its aim is the evaluation of in vitro tests using monocyte derived cells for diagnosis and exclusion of DILI and the potential to use the patient derived-cells for mechanistic investigations of DILI. 4 groups are investigated: 1) donors without liver disease 2) patients who will start a therapy with DILI-potential; 3) DILI patients; 4) patients with liver injuries other than DILI.

Patient history and clinical data are obtained and a single blood sample will be collected after informed consent.

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia
        • Recruiting
        • Gastroenterology, Alfred Health
        • Contact:
  • Germany
    • Bavaria
      • Munich, Bavaria, Germany, 81377
        • Recruiting
        • Liver Center Munich®, Department of Internal Medicine II, LMU University Hospital, Campus Grosshadern
        • Contact:
  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Chinese University of Hong Kong
        • Contact:
        • Principal Investigator:
          • Henry LY Chan, Professor
  • Japan
      • Nagoya, Japan
        • Recruiting
        • Department of Gastroenterology and Hepatology Nagoya University School of Medicine
        • Contact:
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Recruiting
        • Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The groups or cohorts will be selected from patients treated at the LMU University Hospital.

Sampling Method is non-probability sample: patients are invited to volunteer to participate.

Description

Inclusion Criteria:

  • Age ≥ 2 years
  • Informed consent given by the patient or in case of inability to give informed consent informed consent of the legally nominated consultee

Exclusion Criteria:

  • Anemia requiring blood transfusion
  • acute or chronic hepatitis B, C or human immunodeficiency virus infection
  • lack of informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
healthy

donors/patients without liver disease, with and without ongoing drug therapy including buffy coat samples of healthy blood / thrombocyte donors.

After pseudonymisation a detailed history and clinical data are obtained and blood sampling will be performed . Buffy coats are obtained anonymously.
Procedure: Blood sampling
In each group a blood sample of approximately 50 mL will be obtained upon study inclusion.
prior to therapy
History will be obtained and blood sampling will be performed in patients in whom a drug therapy with a drug with DILI potential is planned.
Procedure: Blood sampling
In each group a blood sample of approximately 50 mL will be obtained upon study inclusion.
iDILI
Patients with clinical suspicion of idiosyncratic drug-induced liver injury. After pseudonymisation a detailed history and clinical data are obtained and blood sampling will be performed.
Procedure: Blood sampling
In each group a blood sample of approximately 50 mL will be obtained upon study inclusion.
non DILI
Patients with other forms of liver injury. After pseudonymisation a detailed history and clinical data are obtained and blood sampling will be performed.
Procedure: Blood sampling
In each group a blood sample of approximately 50 mL will be obtained upon study inclusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reflection of individual drug hepatotoxicity in monocyte derived cells
Time Frame: 12 months
After blood sampling, monocyte derived cells will be generated and tested in vitro for the respective compounds in short term and up to 4 weeks. If possible, the patient will have a clinical follow up during routine care to assess liver injury , course and outcome of the disease when applicable.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Andreas Benesic, MD

Collaborators

MetaHeps GmbH

Investigators

  • Principal Investigator: Alexander L Gerbes, Prof. MD, Liver Center Munich®, Internal Medicine II, Ludwig-Maximilians University Hospital, Campus Grosshadern, Munich; Marchioninistr. 15; D81377 Munich, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Anticipated)

March 1, 2020

Study Completion (Anticipated)

August 1, 2022

Study Registration Dates

First Submitted

January 28, 2015

First Submitted That Met QC Criteria

January 28, 2015

First Posted (Estimate)

February 2, 2015

Study Record Updates

Last Update Posted (Actual)

November 26, 2019

Last Update Submitted That Met QC Criteria

November 23, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 055-13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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