Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia

This study has been completed.
Sponsor:
Information provided by:
University of Tehran
ClinicalTrials.gov Identifier:
NCT00515307
First received: August 9, 2007
Last updated: August 28, 2008
Last verified: August 2008
  Purpose

Patients with homozygous familial hypercholesterolemia has very high serum cholesterol levels despite receiving lipid lowering drugs (e.g. statins, etc). Most of such patients die before the age of 20 due to myocardial infarction, etc. Orthotopic liver transplantation (OLT) is an effective treatment for that. Hepatocyte transplantation is an alternative to OLT that may help to overcome the shortage of donor organs. There have been reports of successful treatment of different kinds of metabolic liver disorders by hepatocyte transplantation. The major problem with hepatocyte transplantation is that the source of hepatocytes is very limited. Bone marrow stem cells are the potential source of hepatocytes. In the in-vitro culture system successful and efficient transdifferentiation of mesenchymal stem cells into hepatocytes has been documented. We have already shown that infusion of mesenchymal stem cells is safe and feasible in cirrhosis (Mohamadnejad M, et al. Arch Iran Med 2007; In Press). In this study, 2 patients with homozygous familial hypercholesterolemia will be included. The bone marrow of healthy volunteers with a normal lipid profile will be taken, then bone marrow mesenchymal stem cells (MSCs) will be cultured, and then MSCs will be trans-differentiate into hepatocytes, and the cells will be infused through the portal vein into the patients. The duration of follow up will be 6 months post-transplantation.


Condition Intervention Phase
Hypercholesterolemia, Familial
Procedure: Cellular transplantation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: In-Vitro Transdifferentiation of Mesenchymal Stem Cells to Hepatocytes and Allogenic Transplantation of Hepatocytes to the Patients With Homozygous Familial Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by University of Tehran:

Primary Outcome Measures:
  • Serum cholesterol and LDL levels [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tracking the infused cells [ Time Frame: Month 2 post-transplantation ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: June 2007
Study Completion Date: June 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Procedure: Cellular transplantation
600 million to 1 billion cells will be infused through the portal vein over 30 minutes. Infusion will be done one time.

Detailed Description:

Patients with homozygous familial hypercholesterolemia has very high serum cholesterol levels despite receiving lipid lowering drugs (e.g. statins, etc). Most of such patients die before the age of 20 due to myocardial infarction, etc. Orthotopic liver transplantation (OLT) is an effective treatment and can decrease their serum cholesterol to near normal levels (Bilheimer DW, N Engl J Med 1984; 311:1658-64). Shortage of donor organ is a major problem for OLT. Hepatocyte transplantation is an alternative to OLT that may help to overcome the shortage of donor organ. There have been reports of successful treatment of different kinds of metabolic liver disorders (such as Crigler Najjar Syndrome (Fox IJ, et al. N Engl J Med 1998;338:1422-6), Factor VII deficiency (Dhawan A et al. Transplantation 2004:78:1812-4), Glycogen storage disease type Ia (Muraca M, et al. Lancet 2002;359:317-8), etc) by hepatocyte transplantation. The major problem with hepatocyte transplantation is that the source of hepatocytes is very limited. Bone marrow stem cells are the potential source of hepatocytes. Although, in the in-vivo system there is a controversy that if stem cells transdifferentiate into hepatocytes or fusion of stem cells and hepatocytes occur, however, in the in-vitro culture system successful and efficient transdifferentiation of mesenchymal stem cells into hepatocytes has been documented (Lee KD, et al. Hepatology 2004;40:1275-1284; & Banas A, et al. Hepatology. 2007;46:219-28). We have already shown that infusion of mesenchymal stem cells is safe and feasible in cirrhosis (Mohamadnejad M, et al. Arch Iran Med 2007; In Press). In this study, 2 female patients with homozygous familial hypercholesterolemia will be included. The bone marrow of ABO compatible healthy male volunteers with a normal lipid profile will be taken, then bone marrow mesenchymal stem cells (MSCs) will be cultured, and then MSCs will be trans-differentiate into hepatocytes in the in-vitro culture system. Then the cells will be infused through the portal vein into the patients. The duration of follow up will be 6 months post-transplantation.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Severe hypercholesterolemia unresponsive to lipid lowering agents (e.g. statins)
  • Presence of tendon xanthoma
  • Documentation of homozygous familial hypercholesterolemia by appropriate genetic testing
  • Female gender

Exclusion Criteria:

  • Male gender
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00515307

Locations
Iran, Islamic Republic of
Digestive Disease Research Center, Shariati Hospital, North Kargar Ave.
Tehran, Iran, Islamic Republic of, 14117-13135
Sponsors and Collaborators
University of Tehran
Investigators
Study Chair: Reza Malekzadeh, M.D. Digestive Disease Research Center, Medical Sciences/ Tehran University, Tehran, Iran
Study Chair: Hamid Goorabi, Phd Royan Institute, Tehran, Iran
Principal Investigator: Mehdi Mohamadnejad, M.D. Digestive Disease Research Center, Medical Sciences/ Tehran University, Tehran, Iran
Principal Investigator: Hossein Baharvand, Phd Department of Stem Cells, Royan Institute, Tehran, Iran
  More Information

No publications provided

Responsible Party: Reza Malekzadeh, Digestive Disease Research Center, Medical Sciences/ University of Tehran
ClinicalTrials.gov Identifier: NCT00515307     History of Changes
Other Study ID Numbers: DDRC 85-15
Study First Received: August 9, 2007
Last Updated: August 28, 2008
Health Authority: Iran: Ministry of Health

Keywords provided by University of Tehran:
Hypercholesterolemia, Familial
Bone marrow
Mesenchymal stem cell
Hepatocyte

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Dyslipidemias
Genetic Diseases, Inborn
Hyperlipidemias
Hyperlipoproteinemias
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolic Diseases
Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on October 30, 2014