Clinical trial NCT03585855: Mesenchymal Stem Cell Transplantation in the Treatment of Chronic Antibody Mediated Kidney Graft Rejection (ABMR)
Official title: Autologous Mesenchymal Stem Cell Transplantation in the Treatment of Chronic Antibody Mediated Kidney Graft Rejection (ABMR)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Interventional
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: Slovenian Research Agency
First posted: 2018-07-13
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: comparison with historic control
Primary purpose: TREATMENT

Brief summary: Transplant rejection is one of the biggest limitations in renal transplant procedures, where the kidney can undergo an acute, late acute, or chronic transplant rejection. With the advancement in transplantation protocols, acute survival of renal transplants has improved, but long-term survival is still unsatisfactory, as most of the renal transplants develop chronic graft rejection. Unfortunately, there is little the investigators know when it comes to improving long-term survival of renal transplants. Mesenchymal stem cells (MSC) have been shown to have immunosuppressive and repairing properties. The purpose of this study is to find out whether MSC in combination with standard therapy of antibody mediated rejection (ABMR) are more effective in preventing organ deterioration and maintaining kidney function.

Detailed description: Participants will be assigned to receive the full immunosuppressive therapy indicated to treat chronic ABMR (including plasmapheresis (PF) 7x, intravenous immune globulins 100 mg/kg 7x, corticosteroid) and MSC infusions (2x106cells/kg bw after PF) (Group 1) and be compared to historic controls according to "propensity score matching" (treated with immunosuppressive therapy alone (Group 2)). Patients will undergo MSC infusions at the start of the study after each PF. One year post- infusions, patients will be evaluated and undergo kidney biopsies. Blood collection will occur at regular intervals, serum creatinine and the estimated creatinine clearance will be monthly recorded. The transplanted kidney function and morphology (US Doppler) will be evaluated.

Eligibility criteria: Inclusion Criteria:

* Recipients of a renal allograft, male and female patients age \>18
* The eGF\>20 ml/min/1.73 m2,
* Renal biopsy Criteria: chronic active ABMR.
* Written informed consent, compliant with local regulations.

Exclusion Criteria:

* Recipients of multiple organs.
* Pregnant women.
* Malignant disease in last 5 years
* Active autoimmune disease
* Active infection including hepatitis B, hepatitis C, HIV, or tuberculosis
* Evidence of congestive cardiac failure and/or acute coronary syndrome in past 6 months.
* Evidence of liver disease
* Inadequate compliance to treatment.

Primary outcomes:
measure: Safety of MSC transplantation as assessed by adverse events according to CTCAE Version 5Estimated glomerular filtration rate (eGFR)
timeFrame: 12 months
Secondary outcomes:
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: 12 months
measure: Graft survival rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
affiliation: assist.prof.Željka Večerić-Haler, MDPhD
name: Željka Večerić-Haler, MDPhD
role: PRINCIPAL_INVESTIGATOR
References: