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Efficacy of Invitro Expanded Bone Marrow Derived Allogeneic Mesenchymal Stem Cell Transplantation Via Portal Vein or Hepatic Artery or Peripheral Vein in Patients With Wilson Cirrhosis

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Gulhane Military Medical Academy.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Gulhane Military Medical Academy
Information provided by (Responsible Party):
Murat Kantarcioglu, Gulhane Military Medical Academy
ClinicalTrials.gov Identifier:
NCT01378182
First received: June 20, 2011
Last updated: March 20, 2012
Last verified: March 2012
  Purpose

Wilson's disease is an autosomal recessive genetically inherited disorder of copper metabolism, causing neurological, psychiatric and liver disease. The ATP7B gene on the 13th chromosome is responsible for the disease. Liver has a critical role on copper metabolism. It is the main site of copper accumulation and bile secretion is the only physiologic way of copper elimination. Due to defective production of ceruloplasmin which carries copper, wide amount of free copper precipitates throughout the body but particularly in the liver, eyes and brain. Patients are bound to lifelong chelating agents such as penicillamine, trientine and tetramine dihydrochloride. Unfortunately, these medications may cause severe side-effects such as hypersensitivity reactions, bone marrow suppression, auto-immune disease and sideroblastic anemia. Medical treatment of liver cirrhosis, the last stage of the illness that leads to morbidity and mortality in the Wilson Disease, is difficult. Liver transplantation is still the most effective treatment for the patients with liver cirrhosis in Wilson Disease. However, serious problems are accompanied with liver transplantation. Lack of liver donors, complications during and after the surgery, graft rejection and high costs are the main problems.

There are cells in the human body that are capable to renew themselves and differentiate to a diverse range of specialized cell types. These are called "stem cells". Stem cells can be differentiated to specialized cells in appropriate medias in the laboratory. Recently, the differentiation potential of mesenchymal stem cells into hepatocytes is proved by demonstrating hepatocytes containing Y chromosome in the female who has had bone marrow transplantation from male donors. In many laboratory studies, it is observed that human bone marrow derived mesenchymal stem cells, transplanted to animals with induced liver damage, differentiate into the albumin producing hepatocytes without fusion. By these studies, it is understood that mesenchymal stem cells are more potent than other bone marrow elements in context of differentiation to hepatocytes. Even though the number of studies on human for the same purpose is few, findings are supporting those of animal experiments. Mesenchymal stem cells are non-immunogenic. Safety and feasibility of allogeneic transplantations between individuals without need of immunosuppressive drug regimen are proven. Proofs of correcting metabolic defects by this way are also presented in some publications. For the reasons mentioned above, allogeneic mesenchymal stem cell transplantation is a promising treatment modality especially for the hereditary metabolic diseases. By this way, non-immunogeneic mesenchymal stem cells which have healthy genetic structure, can manufacture the required enzyme, will be repopulated in the damaged tissue and contribute to the clinical improvement.

In this study, mesenchymal stem cells will be derived from healthy volunteer donor's bone marrow and be expanded in-vitro, and then 1 million cells per kg will be infused to patients with liver cirrhosis related to Wilson disease, 50 million cells via hepatic artery and the remaining cells via peripheral vein. It is aimed to enable liver regeneration, decrease fibrosis rate, improve patient's health conditions, increase ceruloplasmin synthesis, ameliorate disorder of copper metabolism, decrease the need for chelating agents, increase living standards of patients, and prolong waiting time for liver transplantation. Finally it is aimed to establish a new and regenerative treatment protocol alternative to liver transplantation. For observation of clinical and laboratory improvement, patients are planned to be monitored by histopathologic examination of liver biopsies before and at 6th month after the treatment, monthly biochemical and hematologic blood tests and periodic radiologic examinations. This is a hopeful, avant garde and sophisticated study which may constitute new horizons in context of cellular therapies.


Condition Intervention
Wilson's Disease
Genetic: allogeneic mesenchymal stem cell transplantation

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Invitro Expanded Bone Marrow Derived Allogeneic Mesenchymal Stem Cell Transplantation Via Portal Vein or Hepatic Artery or Peripheral Vein in Patients With Wilson Cirrhosis

Resource links provided by NLM:


Further study details as provided by Gulhane Military Medical Academy:

Primary Outcome Measures:
  • differantiation of transplanted mesenchymal stem cells to hepatocytes in post treatment liver biopsies [ Time Frame: liver biopsies performed at sixth month after mesenchymal stem cell transplantation ] [ Designated as safety issue: Yes ]
    all patients will be transplanted bone marrow derived mesenchymal stem cells belonging to the opposite sex in order to genetically determine the mature hepatocyte


Estimated Enrollment: 10
Study Start Date: April 2011
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: allogeneic mesenchymal stem cell transplantation
    1.000.000(one million) cells/kg, IV (1/2 of dose in the Peripheral vein and 1/2 of dose into the right hepatic artery)
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical, radiologic and pathologically proven Wilson's Disease with hepatic presentation
  • Patients with no hepatic malignancies
  • No co-existing serious respiratory and/or cardiovascular morbidities
  • Patients who approved to join the study group with informed and written consent
  • Patients with platelet count more than 30.000/mm3

Exclusion Criteria:

  • Clinical diagnosis of Wilson's Disease with neuropsychiatric presentation
  • Current alcohol consumption
  • Patients who have acute or chronic viral hepatitis infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01378182

Locations
Turkey
Department of Gastroenterology; Gulhane Military Medical Academy Recruiting
Ankara, Turkey, 06018
Contact: Murat KANTARCIOGLU, MD    +90 532 5607207    kantarci@hotmail.com   
Sponsors and Collaborators
Murat Kantarcioglu
Gulhane Military Medical Academy
  More Information

No publications provided

Responsible Party: Murat Kantarcioglu, Gulhane Military Medical Academy
ClinicalTrials.gov Identifier: NCT01378182     History of Changes
Other Study ID Numbers: 110S153
Study First Received: June 20, 2011
Last Updated: March 20, 2012
Health Authority: Turkey: Ministry of Health
Turkey: Ethics Committee

Keywords provided by Gulhane Military Medical Academy:
Transplantation,Stem Cell
Wilson's Disease

Additional relevant MeSH terms:
Hepatolenticular Degeneration
Basal Ganglia Diseases
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Digestive System Diseases
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Liver Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on November 25, 2014