Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01745731
Other study ID # CMMo/RH/2009
Secondary ID 2009-017793-20
Status Completed
Phase Phase 2
First received December 3, 2012
Last updated December 11, 2015
Start date March 2011
Est. completion date December 2015

Study information

Verified date December 2015
Source Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Contact n/a
Is FDA regulated No
Health authority Spain: Spanish Agency of Medicines
Study type Interventional

Clinical Trial Summary

This is a randomized controlled trial in which the safety and feasibility of cell therapy medicinal product shall be measured by comparing the variables of the response after treatment compared to baseline prior to implementation. Secondarily the results obtained are compared with each of the study groups.

Patients will receive concomitant basic pharmacological treatment for maintaining liver function.

All patients will be equally medically treated. The hypothetic test is to propose mononuclear cells from the bone marrow infused in the territory hepatic portal remaining segments (II and III) to be performed while contralateral portal embolization provides progenitor cells hepatic regenerative capacity that would shorten the time of liver regeneration and increase residual volume, facilitating the realization of an extended hepatectomy with greater assurance of maintaining proper residual function and adequate surgical margins.


Description:

The study population corresponds to patients with hepatic space occupying lesion that require extended hepatic resection and in which the residual liver volume is insufficient to ensure liver function as well as required safety margins after resection.

The study population will consist of a total of 65 patients divided into two groups:

Study group: patients with hepatic space occupying lesion requiring an extended hepatic resection to those who are undergoing preoperative embolization segments portal intraportal affections and application of bone marrow cells.

Control group: patients with hepatic space occupying lesion that require an extended liver resection and who were performed preoperatively embolization portal of the affected segments.

The distribution of cases / controls will be 1/1. Patients in study group before surgery as well as portal embolization of the affected by the injury, will receive the experimental treatment being tested. Autologous bone marrow will be extracted by aspiration of the iliac crest under local anesthesia, and then the mononuclear cells (mo-MNCs) will be separated by density gradient centrifugation on Ficoll by an automatic procedure in the Laboratory for Cell Therapy.

In the control group patients will be held an embolization of liver segments in which are located the lesion.

It is estimated that the inclusion period is approximately 24 months plus the follow-up of each patient twelve months. Thus the total duration of the study will be about thirty-six months from the entry of the first patient until the end of the monitoring period of the last patient included.

The main objective is to evaluate the safety and feasibility of autologous bone marrow mononuclear cells as autologous liver regeneration enhancer, administered intraportal before surgery in patients with liver space occupying lesion that require extended hepatic resection and in which the residual liver volume is insufficient to ensure liver function and safety margins required after the resection.

Secondary objectives:

- Complications from regenerative therapy and / or study procedures.

- Increased volume obtained after applying the procedures of liver regeneration after surgery.

- The percentage of resections that has allowed liver regeneration.

- The liver functional status after surgery.

- The resection margins free of tumor.

Evaluation Methods:

Radiological assessment of liver volumes. Analytical evaluation of markers of regeneration.


Recruitment information / eligibility

Status Completed
Enrollment 13
Est. completion date December 2015
Est. primary completion date January 2015
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. - Patients of both sexes aged = 18 years.

2. - Standard analytical parameters, defined by:

- Leukocytes = 3000

- Neutrophils = 1500

- Platelets = 100,000

- Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) = 1.5 standard range institution

- creatinine = 1.5 mg / dl

3. - Patients with liver space occupying lesion (LOE) that require extended hepatic resection.

Patient selection should be cautious, covering basically 5 types of liver damage which must be submitted prior to liver volumetry:

- Metastatic Disease subsidiary right hepatectomy extended to segment IV

- Metastatic Disease subsidiary right hepatectomy with suspected diseased liver (neoadjuvant chemotherapy) (in cases of doubt may be used liver function test "indocyanine green")

- Bilobar liver metastases with multiple nodules in the right lobe and more than 3 nodules greater than 30 mm in the left hepatic lobe (LHI) will perform lumpectomies the LHI + right portal branch ligation (or postoperative percutaneous embolization) in order to make right hepatectomy 4-6 weeks ("two stage" surgery)

- Subsidiary Hepatocarcinoma extended right hepatectomy

- Liver Injury benign / malignant (Hemangiomas, hydatid cysts or liver tumors / primary bile hepatoblastoma), which by extension threatens the viability of the remaining liver tissue.

4 - Patients give their written informed consent for participation in the study and provide sufficient guarantees adherence to protocol according to the opinion of the investigator in charge of the patient care.

Exclusion Criteria:

1. Different tumor records current disease or any disease hematologic.

2. Patients with uncontrolled hypertension.

3. Severe heart failure (NYHA IV).

4. Patients with malignant ventricular arrhythmias or unstable angina.

5. Diagnosis of deep vein thrombosis in the previous 3 months.

6. Adjunctive therapy including hyperbaric oxygen, vasoactive substances, agents or angiogenesis inhibitors against Cox-II.

7. BMI> 40 kg/m2.

8. Patients with alcoholic with active alcoholism.

9. Proliferative retinopathy.

10. Concomitant disease that reduces life expectancy to less than a year.

11. Difficulty in monitoring.

12. Heart failure or ejection fraction (EF) <30%.

13. Stroke or myocardial infarction within the last 3 months.

14. Pregnant women or women of childbearing age who do not have adequate contraception.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Other:
Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments.
Proceeds to selective application of stem cells in the portal branches of segments II and III as 10 ml aliquots of taking a time of 4 minutes between each application.

Locations

Country Name City State
Spain University Hospital Virgen del Rocio Sevilla

Sponsors (2)

Lead Sponsor Collaborator
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud Iniciativa Andaluza en Terapias Avanzadas

Country where clinical trial is conducted

Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of adverse events and serious adverse events First 24 hours after administration of the mo-MNC, and monitoring at weeks 2,4 and 6 after drug administration of cell therapy. 6 after drug administration of cell therapy. Yes
Secondary Changes in volume hepatic after application of hepatic regeneration procedures before surgery. 12 months No
See also
  Status Clinical Trial Phase
Completed NCT01678937 - Immune Tolerance and Alloreactivity in Liver Transplant Recipients on Different Monotherapy Immunosuppressive Agents N/A
Completed NCT03781414 - Study of Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in Liver Transplant Recipients With Additional 12-month Follow-up and Long-term Extension Phase 2
Recruiting NCT02260375 - MSC Therapy in Liver Transplantation Phase 1
Not yet recruiting NCT04514666 - VOCs in Kidney and Liver Transplants N/A
Not yet recruiting NCT05335551 - TRU-IMMUNO: Optimizing Liver Immunosuppression
Enrolling by invitation NCT05082077 - Global Utilization And Registry Database for Improved preservAtion of doNor Livers
Completed NCT06060808 - Role of NFKBIA and PTPN22 Genes Polymorphism in Acute Rejection Susceptibility After Living Donor Liver Transplantation in Egyptian Patients.
Completed NCT03874286 - The TOGETHER Project - Liver
Completed NCT04789213 - Mortality, Morbidity and Risk Factors of Liver Retransplantation
Recruiting NCT06400771 - Safety of DNP007 in Healthy Subjects Phase 1
Recruiting NCT03603548 - Comparison of Safety and Efficacy of Two Variants of Prolonged - Released Tacrolimus (Advagraf vs. Envarsus ) in Patients After Liver Transplantation : Single Center Randomised Control Trial N/A
Withdrawn NCT03315052 - Budesonide for Immunosuppression After Liver Transplantation to Reduce Side Effects Phase 4
Enrolling by invitation NCT05655273 - Conversion of Maintenance Prograf to Envarsus in Liver Transplant Recipients Phase 4
Active, not recruiting NCT05325073 - Erythropoietin Therapy to Induce Regulatory T Cells in Liver Transplant Recipients Phase 4
Recruiting NCT05707520 - Long-term Benefit of MPA in Liver Transplantation
Recruiting NCT04657562 - The New LC-MS/MS Method for Determination of Unbound Tacrolimus in Plasma
Completed NCT01444079 - Graft Rejection or Tolerance Affected by Serial Change of Anti-donor Lymphocyte Antibody After Liver Transplantation N/A
Active, not recruiting NCT06153641 - Cytokeratin 18 Non-invasive Biomarker for Rejection in Liver Transplant Patients