NCT02108132

Brief Summary

Hemophilia is caused by a single-gene defect resulting in familial bleeding disorder. Small increase in gene products could transform a severe form of hemophilia into a mild one. Stem cells from extrahepatic sources are being considered for clinical applications in liver cell therapy as they possess high in vitro culture potential and could be used in transplant procedures. We studied the differentiation of bone marrow hematopoietic stem cells (BM-HSCs) from hemophilia patients' relatives into factor 8 (FVIII)-producing hepatocyte-like cells aiming to expand patients' donor options for partial replacement of mutant liver cells by healthy cells in hemophilia A patients which could manage the severity of the bleeding disorder. BM-HSCs from hemophilic families will be cultured in short-liquid hepatic induction medium. Appearance of hepatic phenotype will be evaluated by alpha-fetoprotein expression using immunocytochemistry. Functional evaluation of transdifferentiation will be done through detection of albumin synthesis using microalbumin assay kit, factor VIII activity by one-stage clotting assay and expression of FVIII messenger RNA( mRNA) by reverse transcription ( RT-PCR). Inducing the differentiation of BM-HSCs by in-vitro manipulation may become a valuable tool to provide a cell source for hepatocyte transplant procedures for treatment of hemophilia patients.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Aug 2014

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 15, 2014

Completed
2 months until next milestone

First Posted

Study publicly available on registry

April 9, 2014

Completed
4 months until next milestone

Study Start

First participant enrolled

August 1, 2014

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2015

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2016

Completed
Last Updated

April 9, 2014

Status Verified

April 1, 2014

Enrollment Period

1 year

First QC Date

February 15, 2014

Last Update Submit

April 5, 2014

Conditions

Hemophilia

Keywords

hemophiliamesenchymal stem cellsin-vitro transdifferentiation

Outcome Measures

Primary Outcomes (1)

  • Assessment of Safety / Efficacy

    Assessment of vitality, life style and bleeding times of the Patients.

    2 years

Secondary Outcomes (1)

  • Assessment of Coagulation Profile

    2 years

Study Arms (1)

Cellular therapy

EXPERIMENTAL

Cellular therapy : injection of mesenchymal stem cells subjected to hepatogenic induction

Biological: Cellular therapy

Interventions

cellular therapyBIOLOGICAL

bone marrow derived mesenchymal stem cells for normal subjects will be separated and induced to adopt the hepatocyte phenotype then injected through the portal vein to hemophilia patients

Cellular therapy

Eligibility Criteria

Age6 Years - 40 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Laboratory diagnosis of factor 8 deficiency
  • Dependent on exogenous factor 8 therapy

You may not qualify if:

  • Liver disease
  • History of allergy to factor therapy
  • Abnormal spleen by sonography

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Military Medical Academy

Cairo, Cairo Governorate, 11451, Egypt

Location

Related Publications (4)

  • Hughes RD, Mitry RR, Dhawan A. Current status of hepatocyte transplantation. Transplantation. 2012 Feb 27;93(4):342-7. doi: 10.1097/TP.0b013e31823b72d6.

    PMID: 22082820BACKGROUND

  • Wu XB, Tao R. Hepatocyte differentiation of mesenchymal stem cells. Hepatobiliary Pancreat Dis Int. 2012 Aug 15;11(4):360-71. doi: 10.1016/s1499-3872(12)60193-3.

    PMID: 22893462BACKGROUND

  • Vosough M, Moslem M, Pournasr B, Baharvand H. Cell-based therapeutics for liver disorders. Br Med Bull. 2011;100:157-72. doi: 10.1093/bmb/ldr031. Epub 2011 Jul 19.

    PMID: 21771778BACKGROUND

  • Amer ME, El-Sayed SZ, El-Kheir WA, Gabr H, Gomaa AA, El-Noomani N, Hegazy M. Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. Eur J Gastroenterol Hepatol. 2011 Oct;23(10):936-41. doi: 10.1097/MEG.0b013e3283488b00.

    PMID: 21900788BACKGROUND

MeSH Terms

Conditions

Hemophilia A

Interventions

Cell- and Tissue-Based Therapy

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, InheritedBlood Coagulation DisordersHematologic DiseasesHemic and Lymphatic DiseasesCoagulation Protein DisordersHemorrhagic DisordersGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biological TherapyTherapeutics

Study Officials

  • hala Gabr, M.D.

    Cairo University

    PRINCIPAL INVESTIGATOR

  • Wael Abou El-Kheir, M.D.

    Military Medical Academy, Bulgaria

    STUDY CHAIR

Central Study Contacts

Hala Gabr, M.D.

CONTACT

+202-23644460halagabr@yahoo.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

February 15, 2014

First Posted

April 9, 2014

Study Start

August 1, 2014

Primary Completion

August 1, 2015

Study Completion

February 1, 2016

Last Updated

April 9, 2014

Record last verified: 2014-04

Locations

EG(1)