Pediatric Liver TransplantationPhase 1MYSTEP1NCT02957552
Safety and Tolerance of Immunomodulating Therapy With Donor-specific MSC in Pediatric Living-Donor Liver Transplantation
A Phase 1 study testing Mesenchymal Stem Cells in people with Pediatric Liver Transplantation, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
Since the introduction of calcineurin-based immunosuppression, patient and graft survival in pediatric liver transplantation (LT) improved significantly. However, in contrast, calcineurin inhibitor (CNI) toxicity leads to significant morbidity and impairs quality of life for recipients. Read more about this study
- Who is it for?
- Ages 8 weeks to 18 years
- Conditions the study is for
- Pediatric Liver Transplantation
- What is being tested?
- Mesenchymal Stem Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteGermany
- Study dates
- 10 Mar 2017to Dec 2021
- Phase
- Phase 1
- 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 8 weeks to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Written informed consent (patients, both parents and / or legal guardian)
- age ≥ 8 weeks and ≤ 18 years
- undergoing living donor liver transplantation for chronic terminal liver failure
- Body weight > 5kg
Who cannot join
- No suitability of the living-donor
- Pregnant or breastfeeding
- If appropriate: no use of adequate contraception
- Acute liver failure; highly urgent transplantations
- Receiving any form of solid organ retransplantation
- Multi-Organ-Transplantations
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- Active autoimmune disease
- Pre-existing renal failure with eGFR < 50 ml/min/1.73 m2 or requiring hemodialysis
- Reduced pulmonary function (lung function test in children older than 6 years: FEV1 and FVC < 70% of age-appropriate norm) or clinical suspicion of pulmonary disease affecting patient's physical performance, requiring invasive or non-invasive mechanical ventilation.
- History of pulmonary embolism
- Pulmonary hypertension and / or right ventricular load in echocardiography
- Cardiac function: left ventricular shortening fraction (FS) < 25%
- Clinically significant systemic infections
- Critical care treatment like mechanical ventilation, dialysis or vasopressor agents.
- HIV seropositive, HTLV seropositive, Hepatitis B/C seropositive
- Hepato-biliary malignancies or history of any extra-hepatic malignancy
- Thrombophilia
- Budd-Chiari syndrome
- Pre-existent thrombosis of portal vein
- Doppler-sonographic evidence for relevant porto-systemic shunts, like persistent Ductus Venosus
- Cold ischemia time > 90 min
- Known abuse for drugs or alcohol
- Known allergy to DMSO
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Children's Hospital
Tübingen, 72076
Steffen Hartleif, MD, +497071-29 ext. 84711, steffen.hartleif@med.uni-tuebingen.de
About this study
Official title: Safety and Tolerance of Immunomodulating Therapy With Donor-specific Mesenchymal Stem Cells in Pediatric Living-Donor Liver Transplantation, a 24-month, Non-randomized, Open-label, Prospective, Single-center Pilot Trial
Since the introduction of calcineurin-based immunosuppression, patient and graft survival in pediatric liver transplantation (LT) improved significantly. However, in contrast, calcineurin inhibitor (CNI) toxicity leads to significant morbidity and impairs quality of life for recipients. Moreover, CNI cannot prevent long-term allograft inflammation and fibrosis.
Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties potentially promoting allograft tolerance and ameliorating toxicity of exposure to high dose CNI. Previous trials for non-solid organ transplant indications have shown an excellent safety profile of intravenous MSC application. The MYSTEP1 trial aims to investigate safety and benefits portal and intravenous MSC infusion in pediatric LT.
Read the detailed description
Background: Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury.
Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT.
Methods/Design: 7 to 10 children undergoing living-donor pLT will be included in this open-label, prospective pilot trial. A dose of 1 × 106 MSCs/kg body weight will be given at two time points: first by intraportal infusion intraoperatively and second by intravenous infusion on postoperative day 2. In addition, participants will receive standard immunosuppressive treatment. Our primary objective is to assess the safety of intraportal and intravenous MSC infusion in pLT recipients. Our secondary objective is to evaluate efficacy of MSC treatment as measured by the individual need for immunosuppression and the incidence of biopsy-proven acute rejection. We will perform detailed immune monitoring to investigate immunomodulatory effects.
Discussion: Our study will provide information on the safety of donor-derived MSCs in pediatric living-donor liver transplantation and their effect on immunomodulation and graft survival.
- Conditions
- Pediatric Liver Transplantation
- Being tested
- Mesenchymal Stem Cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal Stem CellsBiological
Donor-specific, bone marrow derived mesenchymal stem (stromal) cells
| Study group | Role | What they receive |
|---|---|---|
| Treatment with Mesenchymal Stem Cells | Experimental | Two doses of 1 x 10^6 MSCs/kg body weight:
* first administration intraoperatively via intraportal infusion
* second infusion via intravenous infusion on postoperative day 2 (+/- 1 day)
Standard immunosuppressive treatment consisting of steroids, basiliximab and tacrolimus according to the center's pediatric liver transplantation protocol Receives: Biological: Mesenchymal Stem Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with MYSTEP-score grade 3 and grade 2 (toxicity of MSC infusion)
In order to evaluate and quantifiy acute clinical complications related to MSC infusion, the investigators defined the MYSTEP score, a specific pediatric infusional toxicity scoring system (adapted from MiSOT-I score). The score focusses on description of intraportal, pulmonary and systemic toxicity. For each of these three modalities, degrees of severity between 0 (no treatment emergent adverse event) and 3 (severe treatment emergent adverse event) have been defined.
Measured: 28 days
Number of participants with occurrence of any severe adverse events (SAE)
A particular focus will be on viral infections and reactivation (ADV, HCMV, EBV, Hepatitis B, Hepatitis C and Hepatitis E), bacterial or fungal infections.
Measured: Two years
Graft function after liver transplantation - Number of participants with abnormal liver tests
Graft function after liver transplantation, measured by aminotransferase and gamma glutamyl transferase activity, bilirubin, albumin and INR.
Measured: Two years
Secondary outcomes (4)
Individual need for immunosuppressive medication
measured by tacrolimus trough levels [ng/ml] and prednisolon dosage [mg/kgBW/day]. Tapering of tacrolimus and steroids will be performed according to a step-wise tapering protocol after day 180.
Measured: Two years
Time to first biopsy-proven acute rejection (BPAR)
Protocol liver biopsy will be performed on day 180 post LT. Additional biopsies will be taken whenever clinically necessary.
Measured: Two years
Immune monitoring: donor-specific antibodies (DSA)
[Participants with positive DSA]
Measured: Two years
Patient and graft survival at 1 and 2 years after liver transplantation
[Death, Re-Transplantation]
Measured: up to Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2016 (estimated)
- Study start10 Mar 2017
- Primary completionDec 2019 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Liver TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- 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
- 7 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, PD Dr. Ekkehard Sturm (MD, PhD), University Hospital Tuebingen
- Investigators
- Ekkehard Sturm, MD, PhD, Principal investigator, University Hospital Tuebingen, Germany; Dept. for Pediatric Gastroenterology and Hepatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02957552
- Sponsor's protocol ID
- MYSTEP1
- Other IDs
- 2014-003561-15, 2014
- Acronym
- MYSTEP1
- Status last verified
- Nov 2018
- First submitted
- 2 Nov 2016
- Last updated
- 14 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerance of Immunomodulating Therapy With Donor-specific Mesenchymal Stem Cells in Pediatric Living-Donor Liver Transplantation, a 24-month, Non-randomized, Open-label, Prospective, Single-center Pilot Trial
- ClinicalTrials.gov ID
- NCT02957552
- Acronym / sponsor ID
- MYSTEP1 / MYSTEP1
- Conditions
- Pediatric Liver Transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 7 participants (estimated)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 10 Mar 2017 (actual)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 7 Nov 2016 (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.
Since the introduction of calcineurin-based immunosuppression, patient and graft survival in pediatric liver transplantation (LT) improved significantly. However, in contrast, calcineurin inhibitor (CNI) toxicity leads to significant morbidity and impairs quality of life for recipients. Moreover, CNI cannot prevent long-term allograft inflammation and fibrosis.
Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties potentially promoting allograft tolerance and ameliorating toxicity of exposure to high dose CNI. Previous trials for non-solid organ transplant indications have shown an excellent safety profile of intravenous MSC application. The MYSTEP1 trial aims to investigate safety and benefits portal and intravenous MSC infusion in pediatric LT.
Detailed description
Background: Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury.
Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT.
Methods/Design: 7 to 10 children undergoing living-donor pLT will be included in this open-label, prospective pilot trial. A dose of 1 × 106 MSCs/kg body weight will be given at two time points: first by intraportal infusion intraoperatively and second by intravenous infusion on postoperative day 2. In addition, participants will receive standard immunosuppressive treatment. Our primary objective is to assess the safety of intraportal and intravenous MSC infusion in pLT recipients. Our secondary objective is to evaluate efficacy of MSC treatment as measured by the individual need for immunosuppression and the incidence of biopsy-proven acute rejection. We will perform detailed immune monitoring to investigate immunomodulatory effects.
Discussion: Our study will provide information on the safety of donor-derived MSCs in pediatric living-donor liver transplantation and their effect on immunomodulation and graft survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with Mesenchymal Stem Cells | Experimental | Biological: Mesenchymal Stem CellsTwo doses of 1 x 10^6 MSCs/kg body weight: * first administration intraoperatively via intraportal infusion * second infusion via intravenous infusion on postoperative day 2 (+/- 1 day) Standard immunosuppressive treatment consisting of steroids, basiliximab and tacrolimus according to the center's pediatric liver transplantation protocol |
Who may qualify
- Ages
- 8 weeks to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Written informed consent (patients, both parents and / or legal guardian)
- age ≥ 8 weeks and ≤ 18 years
- undergoing living donor liver transplantation for chronic terminal liver failure
- Body weight > 5kg
Key exclusion criteria (23 listed)
- No suitability of the living-donor
- Pregnant or breastfeeding
- If appropriate: no use of adequate contraception
- Acute liver failure; highly urgent transplantations
- Receiving any form of solid organ retransplantation
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 |
|---|---|---|
| Mesenchymal Stem CellsDonor-specific, bone marrow derived mesenchymal stem (stromal) cells | Biological | Treatment with Mesenchymal Stem Cells |
Primary outcome
Number of participants with MYSTEP-score grade 3 and grade 2 (toxicity of MSC infusion)
Time frame: 28 days
In order to evaluate and quantifiy acute clinical complications related to MSC infusion, the investigators defined the MYSTEP score, a specific pediatric infusional toxicity scoring system (adapted from MiSOT-I score). The score focusses on description of intraportal, pulmonary and systemic toxicity. For each of these three modalities, degrees of severity between 0 (no treatment emergent adverse event) and 3 (severe treatment emergent adverse event) have been defined.
Number of participants with occurrence of any severe adverse events (SAE)
Time frame: Two years
A particular focus will be on viral infections and reactivation (ADV, HCMV, EBV, Hepatitis B, Hepatitis C and Hepatitis E), bacterial or fungal infections.
Graft function after liver transplantation - Number of participants with abnormal liver tests
Time frame: Two years
Graft function after liver transplantation, measured by aminotransferase and gamma glutamyl transferase activity, bilirubin, albumin and INR.
4 secondary outcomes
Individual need for immunosuppressive medication
Time frame: Two years
Time to first biopsy-proven acute rejection (BPAR)
Time frame: Two years
Immune monitoring: donor-specific antibodies (DSA)
Time frame: Two years
Patient and graft survival at 1 and 2 years after liver transplantation
Time frame: up to Two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2018.
- Individual participant dataSharing planned: No
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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.
Ekkehard Sturm, MD, PhD principal investigator
University Hospital Tuebingen, Germany; Dept. for Pediatric Gastroenterology and Hepatology
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 Mesenchymal Stem Cells in people with Pediatric Liver Transplantation, run by University Hospital Tuebingen 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 4 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 14 Nov 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Steffen Hartleif, MD (+49-7071-29-0 ext. 81339, steffen.hartleif@med.uni-tuebingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with MYSTEP-score grade 3 and grade 2 (toxicity of MSC infusion) (time frame: 28 days). The study lists 3 primary outcomes in all. 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 Nov 2018.