Hepatocyte Matrix Implant Study Indonesia (HMIIndo)

Intracorporeal Autologous Hepatocyte Matrix Implant: A New Tissue Engineering Procedure for Treatment of Hepatic Disease

This clinical investigation of the hepatocyte matrix implant is an evaluation blinded non-randomized and monocentric pilot study of Phase I, which is conducted as a therapeutic investigation. Randomization is not possible due to ethical and practical reasons. This study has already been approved in Switzerland and has been adapted to Indonesian Law and disease.

This new treatment procedure has already been successfully used on the basis of compassionate use in Germany. The hepatocyte matrix implant is a new patented procedure consisting of bio-matrix technology. A formaldehyde-free special matrix consisting of self-dissolving polymers is applied as a carrier substance and is cultivated with human autologous cells using a special technique. Clinically the bio artificial liver replacement tissue for patients with end-stage hepatic disease has been developed as a first application. In this procedure autologous hepatocytic tissue and pancreatic tissue is removed (liver resection and pancreatic biopsy) from the patient in a first surgical procedure. The tissue is sent to a specialized Cell Culture Laboratory. The laboratory is GMP certified for this procedure. The cells are processed according to SOPs in a special perfusion procedure and prepared on several platelets of matrices (platelets of 20 mm diameter and 4mm thickness). After completion of the laboratory process the bio tissues are implanted into the mesentery of the small intestine during a second operation. The cells are growing controlled on the matrix, take on the capillaries of the patient and thus connect to the blood circulation. The implanted cells multiply by a specific factor and independently take over the metabolic function of the original liver after two to four weeks. In the following process the carrier matrix dissolves completely and implanted cells develop into liver cell tissue.

Study Overview

• Status: Unknown
• Conditions: Liver Cirrhosis; Chronic Liver Disease; Liver Insufficiency
• Intervention / Treatment: Procedure: Hepatocyte Matrix Implant

Detailed Description

This new treatment procedure has already been successfully used on the basis of individual treatment in Germany. The hepatocyte matrix implant is a new patented procedure consisting of bio-matrix technology. A formaldehyde-free special matrix consisting of self-dissolving polymers is applied as a carrier substance and is cultivated with human autologous cells using a special technique. Clinically the bio artificial liver replacement tissue for patients with end-stage hepatic disease has been developed as a first application. In this procedure autologous hepatocytic tissue and pancreatic tissue is removed (liver resection and pancreatic biopsy) from the patient in a first surgical procedure. The tissue is sent to a specialized Cell Culture Laboratory. The laboratory is GMP certified for this procedure. The cells are processed according to SOPs in a special perfusion procedure and prepared on several platelets of matrices (platelets of 20 mm diameter and 4mm thickness). After completion of the laboratory process the bio tissues are implanted into the mesentery of the small intestine during a second operation. The cells are growing controlled on the matrix, take on the capillaries of the patient and thus connect to the blood circulation. The implanted cells multiply by a specific factor and independently take over the metabolic function of the original liver after two to four weeks. In the following process the carrier matrix dissolves completely and implanted cells develop into liver cell tissue.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Suryadi The, Dr, MD; Phone Number: +62 8129204193; Email: sury4d1md@gmail.com
• Study Contact Backup: Name: Hans U Baer, Prof MD; Phone Number: +41 387 30 70; Email: hans.baer@baermed.ch

Study Locations

• Indonesia
  • Jakarta, Indonesia, 14250
    • Recruiting
    • R.S. Gading Pluit
    • Sub-Investigator: Suryadi The, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• endstage liver disease
• stable and non-improving liver condition for at least 3 month
• alcoholic liver cirrhosis: proven alcohol abstinence for 6 month or more
• patient in bad general condition

Exclusion Criteria:

• pregnancy
• drug addiction (except alcohol)
• psychiatric disease
• HIV positive
• sepsis
• peritoneal carcinosis
• hereditary liver disease
• acute liver failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: surgery; chronic liver insufficiency, cirrhosis	Procedure: Hepatocyte Matrix Implant; Open surgical procedure with biopsy of liver tissue and pancreatic tissue for proceeding in institutional GMP laboratory. Implantation of autologous hepatocytes and islet cells on scaffolds into the small bowel mesentery. Usually 10 to 20 implants are used.; Other Names: Hepatocyte matrix implantation; Hepatocyte scaffold implantation; Cell matrix implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of clinical and laboratory parameters of liver function	Evaluation of clinical parameters MELD, CHILD, Asictes, portal hypertension in comparison of values measured 3 and 6 months before operation Evaluation of laboratory parameters Bilirubin, ASAT, ALAT, alkaline phosphatase, cholinesterase, albumin, total protein	6 months

Collaborators and Investigators

• Sponsor: Baermed
• Investigators: Principal Investigator: Hans U Baer, Prof, MD, Baermed, RS Gading Pluit, UNTAR

Publications and helpful links

General Publications

• Hendrawan S, Lheman J, Nuraeni, Weber U, Baer HU. Hepatocyte and Islet Cell Cotransplantation on Poly-L-Lactide Matrix for the Treatment of Liver Cirrhosis. Int J Hepatol. 2020 Oct 13;2020:5410359. doi: 10.1155/2020/5410359. eCollection 2020.

Helpful Links

• Baermed Centre for Abdominal Surgery, Zurich, Switzerland

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Anticipated): December 1, 2011
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: April 11, 2011
• First Submitted That Met QC Criteria: April 13, 2011
• First Posted (Estimate): April 14, 2011

Study Record Updates

• Last Update Posted (Estimate): April 14, 2011
• Last Update Submitted That Met QC Criteria: April 13, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Liver cirrhosis; Hepatocyte; Scaffold; Liver insufficiency; Matrix
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Failure; Hepatic Insufficiency; Liver Cirrhosis
• Other Study ID Numbers: Baermed 002