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

NCT00515307 | Completed Phase 1 DMC

• 1 other identifier: DDRC 85-15
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypercholesterolemia, Familial

Keywords

Hypercholesterolemia, Familial; Bone marrow; Mesenchymal stem cell; Hepatocyte

Outcome Measures

Primary Outcomes (1)

• Serum cholesterol and LDL levels

  6 Months

Secondary Outcomes (1)

• Tracking the infused cells

  Month 2 post-transplantation

Study Arms (1)

A

EXPERIMENTAL

Procedure: Cellular transplantation

Interventions

Cellular transplantation PROCEDURE

600 million to 1 billion cells will be infused through the portal vein over 30 minutes. Infusion will be done one time.

A

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Male gender

Sponsors & Collaborators

• University of Tehran: lead

Study Sites (1)

Digestive Disease Research Center, Shariati Hospital, North Kargar Ave.

Tehran, 14117-13135, Iran

Location

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Reza Malekzadeh, M.D.

  Digestive Disease Research Center, Medical Sciences/ Tehran University, Tehran, Iran

  STUDY CHAIR

• Hamid Goorabi, Phd

  Royan Institute, Tehran, Iran

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 9, 2007
• First Posted: August 13, 2007
• Study Start: June 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: June 1, 2008
• Last Updated: August 29, 2008

Record last verified: 2008-08

Locations

IR (1)