Liver Transplant RejectionPhase 2NCT01745731
Cell Infusion Intraportal Autologous Bone Marrow Mononuclear as Enhancer of Liver Regeneration
A Phase 2 study testing Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments. in people with Liver Transplant Rejection, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplant Rejection
- What is being tested?
- Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteSpain
- Study dates
- Mar 2011to Dec 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- - Patients of both sexes aged ≥ 18 years.
- - Standard analytical parameters, defined by:
- Leukocytes ≥ 3000
- Neutrophils ≥ 1500
- Platelets ≥ 100,000
- Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 1.5 standard range institution
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- creatinine ≤ 1.5 mg / dl
- - 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.
Who cannot join
- Different tumor records current disease or any disease hematologic.
- Patients with uncontrolled hypertension.
- Severe heart failure (NYHA IV).
- Patients with malignant ventricular arrhythmias or unstable angina.
- Diagnosis of deep vein thrombosis in the previous 3 months.
- Adjunctive therapy including hyperbaric oxygen, vasoactive substances, agents or angiogenesis inhibitors against Cox-II.
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- BMI> 40 kg/m2.
- Patients with alcoholic with active alcoholism.
- Proliferative retinopathy.
- Concomitant disease that reduces life expectancy to less than a year.
- Difficulty in monitoring.
- Heart failure or ejection fraction (EF) <30%.
- Stroke or myocardial infarction within the last 3 months.
- Pregnant women or women of childbearing age who do not have adequate contraception.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Trial Phase II Multicenter Open Randomized Trial of the Therapeutic Use of Cells Intraportal Infusion of Autologous Bone Marrow Mononuclear as Enhancing Liver Regeneration Prior to Performing Extended Hepatic Resection.
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.
Read the detailed 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.
- Conditions
- Liver Transplant Rejection
- Being tested
- Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments.Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Patients with hepatic space occupying lesion requiring an extended hepatic resection to those who were preoperatively performed a Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments. Receives: Other: Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments. |
| Control | No intervention | Patients with hepatic space occupying lesion that require an extended liver resection that were performed preoperatively portal embolization of the affected segments. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 after drug administration of cell therapy.
Secondary outcomes (1)
Changes in volume hepatic after application of hepatic regeneration procedures before surgery.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2012 (estimated)
- Study startMar 2011
- Primary completionJan 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver Transplant RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
- Sponsor type
- University, hospital or other
- Collaborators
- Iniciativa Andaluza en Terapias Avanzadas
- Responsible party
- Sponsor
- Investigators
- Francisco Javier Padillo, MD, Principal investigator, Head of General and Digestive Surgery, University Hospital Virgen del RocioAntonio Galindo, MD, Principal investigator, Head of General and Digestive Surgery, University Hospital Nuestra Señora de ValmeDaniel Garrote, MD, Principal investigator, Section Chief of General Surgery, University Hospital Virgen de las NievesSebastian Rufian, MD, Principal investigator, Head of General and Digestive Surgery, University Hospital Reina SofiaFrancisco Javier Padillo, MD, Study chair, Head of General and Digestive Surgery, University Hospital Virgen del Rocio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01745731
- Sponsor's protocol ID
- CMMo/RH/2009
- Other IDs
- 2009-017793-20, 2009
- Status last verified
- Dec 2015
- First submitted
- 3 Dec 2012
- Last updated
- 14 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial Phase II Multicenter Open Randomized Trial of the Therapeutic Use of Cells Intraportal Infusion of Autologous Bone Marrow Mononuclear as Enhancing Liver Regeneration Prior to Performing Extended Hepatic Resection.
- ClinicalTrials.gov ID
- NCT01745731
- Acronym / sponsor ID
- CMMo/RH/2009
- Conditions
- Liver Transplant Rejection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y SaludUniversity, hospital or other
- Collaborators
- Iniciativa Andaluza en Terapias Avanzadas
- Study start
- Mar 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 10 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Other: Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments.Patients with hepatic space occupying lesion requiring an extended hepatic resection to those who were preoperatively performed a Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments. |
| Control | No intervention | –Patients with hepatic space occupying lesion that require an extended liver resection that were performed preoperatively portal embolization of the affected segments. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- - Patients of both sexes aged ≥ 18 years.
- - Standard analytical parameters, defined by:
- - 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
Key exclusion criteria (14 listed)
- Different tumor records current disease or any disease hematologic.
- Patients with uncontrolled hypertension.
- Severe heart failure (NYHA IV).
- Patients with malignant ventricular arrhythmias or unstable angina.
- Diagnosis of deep vein thrombosis in the previous 3 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Experimental |
Primary outcome
Number of adverse events and serious adverse events
Time frame: 6 after drug administration of cell therapy.
First 24 hours after administration of the mo-MNC, and monitoring at weeks 2,4 and 6 after drug administration of cell therapy.
1 secondary outcome
Changes in volume hepatic after application of hepatic regeneration procedures before surgery.
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2015.
- Andalusian Molecular Biology and Regenerative Medicine CentreLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francisco Javier Padillo, MD principal investigator
Head of General and Digestive Surgery, University Hospital Virgen del Rocio
Antonio Galindo, MD principal investigator
Head of General and Digestive Surgery, University Hospital Nuestra Señora de Valme
Daniel Garrote, MD principal investigator
Section Chief of General Surgery, University Hospital Virgen de las Nieves
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cell infusion intraportal mononuclear bone marrow autologous and portal embolization of the affected segments. in people with Liver Transplant Rejection, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events and serious adverse events (time frame: 6 after drug administration of cell therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2015.