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Sponsored by: |
University of Tehran |
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Information provided by: | University of Tehran |
ClinicalTrials.gov Identifier: | NCT00515307 |
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 |
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Hypercholesterolemia, Familial |
Procedure: Cellular transplantation |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | In-Vitro Transdifferentiation of Mesenchymal Stem Cells to Hepatocytes and Allogenic Transplantation of Hepatocytes to the Patients With Homozygous Familial Hypercholesterolemia |
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 |
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A: Experimental |
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.
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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.
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Iran, Islamic Republic of | |
Digestive Disease Research Center, Shariati Hospital, North Kargar Ave. | |
Tehran, Iran, Islamic Republic of, 14117-13135 |
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 |
Responsible Party: | Digestive Disease Research Center, Medical Sciences/ University of Tehran ( Reza Malekzadeh ) |
Study ID Numbers: | DDRC 85-15 |
Study First Received: | August 9, 2007 |
Last Updated: | August 28, 2008 |
ClinicalTrials.gov Identifier: | NCT00515307 History of Changes |
Health Authority: | Iran: Ministry of Health |
Hypercholesterolemia, Familial Bone marrow Mesenchymal stem cell Hepatocyte |
Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors Metabolic Diseases Hyperlipidemias Genetic Diseases, Inborn Hyperlipoproteinemia Type II |
Hypercholesterolemia, Autosomal Dominant Metabolic Disorder Hypercholesterolemia Dyslipidemias Hyperlipoproteinemias Lipid Metabolism Disorders |
Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors Metabolic Diseases Hyperlipidemias Genetic Diseases, Inborn |
Hyperlipoproteinemia Type II Hypercholesterolemia Hyperlipoproteinemias Dyslipidemias Lipid Metabolism Disorders |