Safety and Tolerance of Immunomodulating Therapy With Donor-specific MSC in Pediatric Living-Donor Liver Transplantation

Last updated: November 9, 2018
Sponsor: University Hospital Tuebingen
Overall Status: Active - Recruiting

Phase

1

Condition

Organ Transplant - Pediatric

Liver Transplantation

Treatment

N/A

Clinical Study ID

NCT02957552
MYSTEP1
2014-003561-15
  • Ages 8-18
  • All Genders

Study 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. 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Written informed consent (patients, both parents and / or legal guardian)

  2. age ≥ 8 weeks and ≤ 18 years

  3. undergoing living donor liver transplantation for chronic terminal liver failure

  4. Body weight > 5kg

Exclusion

Exclusion Criteria:

  1. No suitability of the living-donor

  2. Pregnant or breastfeeding

  3. If appropriate: no use of adequate contraception

  4. Acute liver failure; highly urgent transplantations

  5. Receiving any form of solid organ retransplantation

  6. Multi-Organ-Transplantations

  7. Active autoimmune disease

  8. Pre-existing renal failure with eGFR < 50 ml/min/1.73 m2 or requiring hemodialysis

  9. Reduced pulmonary function (lung function test in children older than 6 years: FEV1and FVC < 70% of age-appropriate norm) or clinical suspicion of pulmonary diseaseaffecting patient's physical performance, requiring invasive or non-invasivemechanical ventilation.

  10. History of pulmonary embolism

  11. Pulmonary hypertension and / or right ventricular load in echocardiography

  12. Cardiac function: left ventricular shortening fraction (FS) < 25%

  13. Clinically significant systemic infections

  14. Critical care treatment like mechanical ventilation, dialysis or vasopressor agents.

  15. HIV seropositive, HTLV seropositive, Hepatitis B/C seropositive

  16. Hepato-biliary malignancies or history of any extra-hepatic malignancy

  17. Thrombophilia

  18. Budd-Chiari syndrome

  19. Pre-existent thrombosis of portal vein

  20. Doppler-sonographic evidence for relevant porto-systemic shunts, like persistentDuctus Venosus

  21. Cold ischemia time > 90 min

  22. Known abuse for drugs or alcohol

  23. Known allergy to DMSO

Study Design

Total Participants: 7
Study Start date:
March 10, 2017
Estimated Completion Date:
December 31, 2021

Study 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.

Connect with a study center

  • University Children's Hospital

    Tuebingen, 72076
    Germany

    Active - Recruiting

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