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

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ClinicalTrials.gov Identifier: NCT02353455
Recruitment Status : Recruiting
First Posted : February 2, 2015
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Andreas Benesic, MD, Ludwig-Maximilians - University of Munich

Brief Summary:
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.

Condition or disease Intervention/treatment
Drug-induced Disorder of Liver Adverse Reaction to Drug Procedure: Blood sampling

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.


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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cells of Monocytic Origin as Surrogate Markers for Individual Drug Effects and Hepatotoxicity
Study Start Date : March 2013
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : August 2022

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.




Primary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples Without DNA
PBMC samples, monocyte derived cells


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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02353455


Contacts
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Contact: Andreas Benesic, MD +49 89 44007 ext 3130 andreas.benesic@med.uni-muenchen.de

Locations
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Australia, Victoria
Gastroenterology, Alfred Health Recruiting
Melbourne, Victoria, Australia
Contact: Joanne Mitchell, CTC    (03) 9076 2583    J.Mitchell@alfred.org.au   
Germany
Liver Center Munich®, Department of Internal Medicine II, LMU University Hospital, Campus Grosshadern Recruiting
Munich, Bavaria, Germany, 81377
Contact: Andreas Benesic, MD    +49 89 44007 ext 3130    andreas.benesic@med.uni-muenchen.de   
Hong Kong
Chinese University of Hong Kong Recruiting
Hong Kong, Hong Kong
Contact: Peter Tse       petse@cuhk.edu.hk   
Principal Investigator: Henry LY Chan, Professor         
Japan
Department of Gastroenterology and Hepatology Nagoya University School of Medicine Recruiting
Nagoya, Japan
Contact: Masatoshi Ishigami, MD    +81-52-744-2190    masaishi@med.nagoya-u.ac.jp   
Korea, Republic of
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine Recruiting
Seoul, Korea, Republic of
Contact: Han Ah Lee, Ass Prof       amelia86@naver.com   
Sponsors and Collaborators
Andreas Benesic, MD
Investigators
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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

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Andreas Benesic, MD, Dr. med., Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT02353455     History of Changes
Other Study ID Numbers: 055-13
First Posted: February 2, 2015    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
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Liver Diseases
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Digestive System Diseases