Liver TransplantationPhase 1NCT01841632
Safety Study of Multipotent Progenitor Cells for Immunomodulation Therapy After Liver Transplantation
A Phase 1 study testing MultiStem in people with Liver Transplantation, run by Prof. Dr. Marc-H. Dahlke, Ph. D. at 1 site in Germany.
Trial summary
MultiStem ® is a new biological product, manufactured from human stem cells obtained from adult bone marrow. Factors expressed by MultiStem cells are believed to regulate immune system function and augment tissue repair. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Liver Transplantation
- What is being tested?
- MultiStem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2013to Dec 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥18 years of age undergoing allogeneic liver transplantation
- Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Written informed consent prior to any study procedures
Who cannot join
- Known allergies to bovine or porcine products or any other ingredients of the product
- Patients older than 65 years of age
- Patients listed in a high-urgency status that would not allow proper preparation of the study interventions
- Patients receiving a secondary liver graft (Re-Transplantation)
- Double organ transplant recipients
- Pre-existing renal failure that requires or has required hemodialysis within the last year
Show all 14Show fewer
- Pulmonary function: FEV1, FVC, DLCO ≤50% predicted
- Cardiac function: left ventricular ejection fraction ≤50%
- HIV seropositive, varicella virus active infection or any other clinically relevant infection
- History of any malignancy (including lymphoproliferative disease and hepatocellular carcinoma) except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence
- Unstable myocardium (evolving myocardial infarction), cardiogenic shock
- Females of childbearing potential (hormonal status and gynecological consultation required)
- Patients with portal vein thrombosis
- Patients with a history of pulmonary embolism
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Surgery, University Hospital Regensburg
Regensburg, Bavaria, 93053
About this study
Official title: Safety and Feasibility of Multipotent Adult Progenitor Cells for Immunomodulation Therapy After Liver Transplantation: A Phase I Study of the MiSOT Study Consortium
MultiStem ® is a new biological product, manufactured from human stem cells obtained from adult bone marrow. Factors expressed by MultiStem cells are believed to regulate immune system function and augment tissue repair.
Standard of care pharmacological immunosuppression after liver transplantation can achieve reasonable survival of liver grafts and patients. The side effects of this treatment, however, are clinically significant and diminish the overall success of organ transplantation as a curative therapy. It is therefore the objective of this study to implement cellular immunomodulation therapy with MultiStem as an adjunct to standard pharmacological immunosuppression with the ultimate goal of significantly reducing drug-based immunosuppression.
As this is the first study with MultiStem in this subject population it has been designed as a safety and feasibility trial. However, first evidence of a potential benefit for this patient population will be explored cautiously.
- Conditions
- Liver Transplantation
- Being tested
- MultiStem
- Keywords
- Liver transplantation, Allogeneic liver transplantation, Solid organ transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MultiStemDrug
| Study group | Role | What they receive |
|---|---|---|
| MultiStem | Experimental | Dose escalation
Cohort 1
Drug: MultiStem, Dose 1 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3)
Cohort 2
Drug: MultiStem, Dose 2 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3)
Cohort 3
Drug: MultiStem, Dose 3 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3)
Cohort 4
Drug: MultiStem, Dose 4 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3) Receives: Drug: MultiStem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism
- For the description of intraportal toxicity a doppler ultrasound examination will be performed to assess various parameters that describe velocity of flow and flow pattern.
- For pulmonary toxicity the assessment begins with an arterial blood gas. If this reveals pathological findings, a chest X-ray is required for clinical reasons independent of the study enrolment. In addition, clinical data describing the need for postoperative re-intubation will be recorded and the patient is assessed for the occurrence of a pulmonary embolism according to clinical guidelines.
- For systemic toxicity, the occurrence of anaphylactic shock due to standard clinical guidelines is recorded.
Measured: up to day 30 (+10)
Secondary outcomes (3)
Time to First Biopsy-proven Acute Rejection
Per protocol biopsies will be performed on days 1, 4, 10. Additional biopsies will be taken whenever clinically necessary.
Measured: up to day 90 (+/-30)
Evidence Confirming That MultiStem Does Not Promote Malignant Transformation or Tumor Growth
Four additional outpatient visits are planned to further evaluate the study patients (including screening for malignancies).
Measured: up to day 365 (+/-30)
Evaluation of Data From Routine Examinations Following Last Study Visit for Evidence of Long Term Safety From MultiStem Administration
The results of routine examinations, which are necessary for all transplant patients, will be used once a year and analyzed retrospectively.
Measured: up to six years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2013 (estimated)
- Study startApr 2013
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver TransplantationStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof. Dr. Marc-H. Dahlke, Ph. D.
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Regensburg, Healios K.K.
- Responsible party
- Sponsor-investigator, Prof. Dr. Marc-H. Dahlke, Ph. D., University Hospital Regensburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01841632
- Sponsor's protocol ID
- MISOT-I
- Other IDs
- 2009-017795-25, 2009
- Status last verified
- Dec 2017
- First submitted
- 19 Apr 2013
- Last updated
- 17 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Popp FC, Fillenberg B, Eggenhofer E, Renner P, Dillmann J, Benseler V, Schnitzbauer AA, Hutchinson J, Deans R, Ladenheim D, Graveen CA, Zeman F, Koller M, Hoogduijn MJ, Geissler EK, Schlitt HJ, Dahlke MH. Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation--a phase I study (MISOT-I). J Transl Med. 2011 Jul 28;9:124. doi: 10.1186/1479-5876-9-124.
PubMed 21798013Dillmann J, Popp FC, Fillenberg B, Zeman F, Eggenhofer E, Farkas S, Scherer MN, Koller M, Geissler EK, Deans R, Ladenheim D, Loss M, Schlitt HJ, Dahlke MH. Treatment-emergent adverse events after infusion of adherent stem cells: the MiSOT-I score for solid organ transplantation. Trials. 2012 Nov 15;13:211. doi: 10.1186/1745-6215-13-211.
PubMed 23151227
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility of Multipotent Adult Progenitor Cells for Immunomodulation Therapy After Liver Transplantation: A Phase I Study of the MiSOT Study Consortium
- ClinicalTrials.gov ID
- NCT01841632
- Acronym / sponsor ID
- MISOT-I
- Conditions
- Liver Transplantation
- Keywords
- Liver transplantation, Allogeneic liver transplantation, Solid organ transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Prof. Dr. Marc-H. Dahlke, Ph. D.University, hospital or other
- Collaborators
- University Hospital Regensburg, Healios K.K.
- Study start
- Apr 2013 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 26 Apr 2013 (estimated)
- Results
- Posted 17 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
MultiStem ® is a new biological product, manufactured from human stem cells obtained from adult bone marrow. Factors expressed by MultiStem cells are believed to regulate immune system function and augment tissue repair.
Standard of care pharmacological immunosuppression after liver transplantation can achieve reasonable survival of liver grafts and patients. The side effects of this treatment, however, are clinically significant and diminish the overall success of organ transplantation as a curative therapy. It is therefore the objective of this study to implement cellular immunomodulation therapy with MultiStem as an adjunct to standard pharmacological immunosuppression with the ultimate goal of significantly reducing drug-based immunosuppression.
As this is the first study with MultiStem in this subject population it has been designed as a safety and feasibility trial. However, first evidence of a potential benefit for this patient population will be explored cautiously.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MultiStem | Experimental | Drug: MultiStemDose escalation Cohort 1 Drug: MultiStem, Dose 1 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3) Cohort 2 Drug: MultiStem, Dose 2 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3) Cohort 3 Drug: MultiStem, Dose 3 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3) Cohort 4 Drug: MultiStem, Dose 4 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients ≥18 years of age undergoing allogeneic liver transplantation
- Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Written informed consent prior to any study procedures
Key exclusion criteria (14 listed)
- Known allergies to bovine or porcine products or any other ingredients of the product
- Patients older than 65 years of age
- Patients listed in a high-urgency status that would not allow proper preparation of the study interventions
- Patients receiving a secondary liver graft (Re-Transplantation)
- Double organ transplant recipients
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 |
|---|---|---|
| MultiStem | Drug | MultiStem |
Primary outcome
Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism
Time frame: up to day 30 (+10)
* For the description of intraportal toxicity a doppler ultrasound examination will be performed to assess various parameters that describe velocity of flow and flow pattern. * For pulmonary toxicity the assessment begins with an arterial blood gas. If this reveals pathological findings, a chest X-ray is required for clinical reasons independent of the study enrolment. In addition, clinical data describing the need for postoperative re-intubation will be recorded and the patient is assessed for the occurrence of a pulmonary embolism according to clinical guidelines. * For systemic toxicity, the occurrence of anaphylactic shock due to standard clinical guidelines is recorded.
3 secondary outcomes
Time to First Biopsy-proven Acute Rejection
Time frame: up to day 90 (+/-30)
Evidence Confirming That MultiStem Does Not Promote Malignant Transformation or Tumor Growth
Time frame: up to day 365 (+/-30)
Evaluation of Data From Routine Examinations Following Last Study Visit for Evidence of Long Term Safety From MultiStem Administration
Time frame: up to six years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21798013Popp FC, Fillenberg B, Eggenhofer E, Renner P, Dillmann J, Benseler V, Schnitzbauer AA, Hutchinson J, Deans R, Ladenheim D, Graveen CA, Zeman F, Koller M, Hoogduijn MJ, Geissler EK, Schlitt HJ, Dahlke MH. Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation--a phase I study (MISOT-I). J Transl Med. 2011 Jul 28;9:124. doi: 10.1186/1479-5876-9-124.
- Background: PubMed 23151227Dillmann J, Popp FC, Fillenberg B, Zeman F, Eggenhofer E, Farkas S, Scherer MN, Koller M, Geissler EK, Deans R, Ladenheim D, Loss M, Schlitt HJ, Dahlke MH. Treatment-emergent adverse events after infusion of adherent stem cells: the MiSOT-I score for solid organ transplantation. Trials. 2012 Nov 15;13:211. doi: 10.1186/1745-6215-13-211.
Related trials for Liver Transplantation
Not yet recruitingObservational study
Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Not yet recruiting
New Biomarkers for Organ Viability Assessment During Hypothermic Machine Perfusion in Liver Transplantation: the Role of Extemporaneous Histological Examination.
Liver Transplantation (LT), Early Allograft Dysfunction
RecruitingPhase 2
Expanding Liver Transplant Immunosuppression Minimization Via Everolimus
Liver Transplant
RecruitingObservational study
Long-term Follow-up (LTFU) Study of Participants in Any iECURE Protocol Using an Investigational Product (IP)
Ornithine Transcarbamylase Deficiency, Ornithine Transcarbamylase Deficiency Disease
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MultiStem in people with Liver Transplantation, run by Prof. Dr. Marc-H. Dahlke, Ph. D. at 1 site in Germany.
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 3 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: stopped early, as of the sponsor's last update on 17 Aug 2018. 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 Germany. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism (time frame: up to day 30 (+10)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01841632, which also lists 2 linked publications.
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 17 Aug 2018.