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

August 28, 2008 updated by: University of Tehran

In-Vitro Transdifferentiation of Mesenchymal Stem Cells to Hepatocytes and Allogenic Transplantation of Hepatocytes to the Patients With Homozygous Familial Hypercholesterolemia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Iran, Islamic Republic of
      • Tehran, Iran, Islamic Republic of, 14117-13135
        • Digestive Disease Research Center, Shariati Hospital, North Kargar Ave.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Serum cholesterol and LDL levels
Time Frame: 6 Months
6 Months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Tracking the infused cells
Time Frame: Month 2 post-transplantation
Month 2 post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Tehran

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 9, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 9, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 13, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 29, 2008

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2008

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DDRC 85-15

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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