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Intrahepatic Reinfusion of CD133+ Stem Cells in Cirrhotic Patients (Cirrhosis133)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2010 by University of Bologna.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Bologna
ClinicalTrials.gov Identifier:
NCT01025622
First received: December 2, 2009
Last updated: October 28, 2010
Last verified: October 2010
  Purpose

OBJECTIVE(S): Primary:

To assess the safety of the intrahepatic reinfusion of increasing numbers of autologous highly purified CD133+ stem cells (SCs) to patients with end-stage liver disease. Safety will be evaluated as the incidence of adverse event (graded according to WHO) and clinically significant abnormal laboratory value following reinfusion of SCs.

Secondary:

To assess the feasibility of the immunomagnetic selection of autologous CD133+ cells collected with leukapheresis from the peripheral blood (PB) of patients with end-stage liver disease, previously mobilized with G-CSF. To assess the effects of the intrahepatic reinfusion of highly purified CD133+ cells on residual hepatic function of the patients.

STUDY DESIGN:

Twelve patients will be enrolled. At first, G-CSF at 7.5µg/Kg/b.i.d. will be administered subcutaneously (sc) from day 1 until the completion of peripheral blood stem cells (PBSC) collection. Harvest of bone marrow (BM)-derived PBSC will begin on day + 4 only if the concentration of CD133+ cells is > 8/uL and will be continued until the collection of the target cell dose: 0.5 x 106 CD133+ cells/Kg for the first 2 cohorts of patients; 1 x 106 CD133+ cells/Kg for cohort 3 and 2 x 106 CD133+ cells/Kg for cohort 4 (see below for definitions). PB mononuclear cells obtained from mobilized standard-volume leukapheresis will be incubated with Macs colloidal superparamagnetic CD133 microbeads and CliniMacs device will be used for the positive selection of CD133+ cells under good manufacturing practice (GMP) conditions. Cryopreservation and storage in liquid nitrogen will be performed according to standard procedures. At least 4 weeks after SC mobilization and collection, up to 40 mL of single cell suspension of highly purified autologous CD133+ cells, obtained after rapid thawing, will be infused through the hepatic artery by transfemoral or transbrachial arteriography. Infusion time will be lower than 15ml/min to avoid thrombi formation. The entire procedure will be performed under anesthesiological control. According to modified Fibonacci's increment rule, highly purified G-CSF-mobilized CD133+ cells will be administered to patients starting from 5x104/Kg patient's body weight and increased every 3 patients. The maximum infused cell dose will be 1x106/kg. G-CSF at 5µg/Kg/day will be administered sc for 3 days after the reinfusion of SCs (day 0 to day +2).


Condition Intervention Phase
Liver Cirrhosis
Biological: autologous highly purified CD133+ stem cells (SCs)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Study of Intrahepatic Reinfusion of Highly Purified CD133+ Stem Cells in Patients With End-Stage Liver Disease

Resource links provided by NLM:


Further study details as provided by University of Bologna:

Primary Outcome Measures:
  • Safety: Incidence of adverse events (graded according to WHO). Incidence of clinically significant abnormal laboratory values following reinfusion of highly purified CD133+ cells. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effects of the intrahepatic reinfusion of highly purified CD133+ SCs on residual hepatic function of the patients: Child-Turcotte-Pugh and MELD score. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: October 2009
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: autologous highly purified CD133+ stem cells (SCs)
    Intrahepatic reinfusion in cirrhotic patients
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent
  • Age >18 years
  • Karnofsky score >70% or WHO <1
  • Adequate renal (serum creatinine < 2 mg/dl) and pulmonary (Sat O2 >96%) function
  • Diagnosis of advanced, end-stage liver disease defined by a Mayo Model for End Stage Liver Disease (MELD) score between 17 and 25. Patients with the following liver disease etiologies will be enrolled in the study: chronic viral hepatitis B, chronic viral hepatitis C, chronic viral hepatitis D, alcoholic cirrhosis (without alcohol active consumption), primary sclerosing cholangitis, primary biliary cirrhosis, Wilson's disease, genetic hemochromatosis or iron over-load cirrhosis, cirrhosis due to non alcoholic steato-hepatitis.

Eligibility for orthotopic liver transplantation (OLT) is not a contraindication to enter in the clinical study. Patients in waiting list for OLT transplantation will not be withdrawn and will be transplanted as soon as a suitable donor will become available.Their MELD score will remain that recorded prior SCs infusion in case of improvement following the experimental procedure.

The presence of cirrhosis related symptoms, like ascites, peripheral edema, recurrent gastrointestinal tract bleeding, recurrent encephalopathy do not represent major contraindications to be enrolled into the study.

The patients may be considered eligible when clinically stable.

Exclusion Criteria:

  • HIV positivity
  • Pregnant or nursing females
  • Current uncontrolled infection
  • Intercurrent organ damage
  • Diagnosis of hepatocarcinoma
  • Complete portal thrombosis
  • Severe impairment of coagulative function (PT< 30%, INR>2.5, Platelets < 40x109/L) that would contraindicate arteriography
  • Grade IV splenomegaly
  • Budd-Chiari Syndrome with sovrahepatic vein thrombosis and cirrhosis of unknown origin will not be included in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01025622

Contacts
Contact: Roberto M Lemoli, MD +390516363680 roberto.lemoli@unibo.it
Contact: Pietro Andreone, MD +390516363817 pietro.andreone@unibo.it

Locations
Italy
Azienda Ospedaliera-Universitaria, Policlinico S. Orsola-Malpighi Recruiting
Bologna, Italy, 40138
Contact: Roberto M Lemoli, MD    +390516363680    roberto.lemoli@unibo.it   
Principal Investigator: Roberto M Lemoli, MD         
Azienda Ospedaliera-Universitaria, Policlinico S. Orsola-Malpighi, Active, not recruiting
Bologna, Italy, 40138
Sponsors and Collaborators
University of Bologna
Investigators
Principal Investigator: Roberto M Lemoli, MD University of Bologna
  More Information

Additional Information:
No publications provided

Responsible Party: Roberto M. Lemoli, MD, University of Bologna
ClinicalTrials.gov Identifier: NCT01025622     History of Changes
Other Study ID Numbers: 2009-011783-10
Study First Received: December 2, 2009
Last Updated: October 28, 2010
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University of Bologna:
Stem Cells
Liver Cirrhosis
Cell Therapy

Additional relevant MeSH terms:
Liver Cirrhosis
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on November 25, 2014