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Allogeneic Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients (Neptune)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02387151
Recruitment Status : Completed
First Posted : March 12, 2015
Last Update Posted : July 2, 2019
Information provided by (Responsible Party):
M.E. J. Reinders, Leiden University Medical Center

Brief Summary:
This study will test whether selected allogeneic bone marrow derived MSCs are safe by assessing the composite end point Biopsy Proven Acute Rejection (BPAR)/ graft loss at 12 months.

Condition or disease Intervention/treatment Phase
Rejection Graft Loss Drug: mesenchymal stromal cells Phase 1

Detailed Description:

Kidney transplantation has improved survival and quality of life for patients with end-stage renal disease. However, despite advances in immunosuppressive therapy, long-term allograft survival outcomes have not improved over the last decade.

A promising novel therapeutic immunosuppressive option in the treatment of renal recipients with a profound effect on the fibrosis reaction is the clinical application of mesenchymal stromal cells (MSCs). Allogeneic MSCs offer the advantage of availability for clinical use without the delay required for expansion.

Although it is believed that allo MSCs are immune privileged, they could possibly elicit an anti-donor immune response, which may increase the incidence of rejection/ graft loss and impact the allograft survival on the long term. These safety issues should be studied before further studies are planned with allogeneic MSCs in the transplant setting.

MSCs are infused at a time point when immune suppression is lowered and the kidney is at increased risk for developing immune mediated injury. In addition, a large amount of the kidneys already has signs of fibrosis at this time point and MSCs might reduce the fibrosis which so importantly affects long term survival. MSCs will have no Human Leucocyte Antigen (HLA) sharing with the mismatches of the donor and the recipient should have no antibodies directed to the MSCs to reduce the anti-donor immune respons risk.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients
Actual Study Start Date : March 2015
Actual Primary Completion Date : November 2018
Actual Study Completion Date : November 2018

Arm Intervention/treatment
Experimental: mesenchymal stromal cells
allogeneic mesenchymal stromal cell infusion
Drug: mesenchymal stromal cells
2 doses of 1-2x10^6 allogeneic bone marrow derives MSCs IV per/kg body weight at weeks 25 and 26 after transplantation
Other Names:
  • MSC
  • bone marrow derived mesenchymal stromal cells

Primary Outcome Measures :
  1. biopsy proven acute rejection / graft loss [ Time Frame: 12 months after transplantation ]

Secondary Outcome Measures :
  1. Comparison of fibrosis by quantitative Sirius Red scoring [ Time Frame: Before MSC infusion (week 24 after transplantation) and 6 months after MSC infusion (week 52 after transplantation) ]
  2. Serious adverse events [ Time Frame: 12 months after transplantation ]
  3. Renal function measured by cGFR (MDRD formula) and iohexol clearance [ Time Frame: week 24 after transplantation (before MSC infusion) and 52 after transplantation ]
  4. CMV, BK infection (viremia, disease and syndrome; and subtypes of BK viremia) and other opportunistic infections [ Time Frame: from baseline up to 26 weeks after MSC treatment ]
  5. Development of de novo donor specific antibodies (DSA) and immunological responses [ Time Frame: at baseline, week 24 after transplantation (before MSC treatment) up to week 26 after MSC treatment ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject is willing to participate in the study, must be able to give informed consent and the consent must be obtained prior to any study procedure.
  • Recipients of a first kidney graft from a living-unrelated or non-HLA identical living related donor.
  • Panel Reactive Antibodies (PRA) ≤ 50%.
  • Patients must be able to adhere to the study visit schedule and protocol requirements.
  • If female and of child-bearing age, subject must be non-pregnant, non-breastfeeding, and use adequate contraception.

Exclusion Criteria:

  • Double organ transplant recipient.
  • Biopsy proven acute rejection (according to the Banff criteria) in the 4 weeks before MSC infusion.
  • Patients with evidence of active infection or abscesses (with the exception of an uncomplicated urinary tract infection) before MSC infusion.
  • Patients suffering from hepatic failure.
  • Patients suffering from an active autoimmune disease.
  • A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
  • Use of any investigational drug after transplantation.
  • Documented HIV infection, active hepatitis B, hepatitis C or tuberculosis according to current transplantation inclusion criteria.
  • Subjects who currently an active opportunistic infection at the time of MSC infusion (e.g., herpes zoster [shingles], cytomegalovirus (CMV), Pneumocystis carinii (PCP), aspergillosis, histoplasmosis, or mycobacteria other than tuberculosis, BK) after transplantation.
  • Malignancy (including lymphoproliferative disease) within the past 2-5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence) according to current transplantation inclusion criteria
  • Known recent substance abuse (drug or alcohol).
  • Patients who are recipients of ABO incompatible transplants.
  • Patients with severe total hypercholesterolemia (>7.5 mmol/L) or total hypertriglyceridemia (>5.6 mmol/L) (patients on lipid lowering treatment with controlled hyperlipidemia are acceptable).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02387151

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Leiden University Medical Center
Leiden, Netherlands, 2333 ZA
Sponsors and Collaborators
Leiden University Medical Center
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Principal Investigator: Marlies EJ Reinders, MD/PhD Leiden University Medical Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: M.E. J. Reinders, MD/PhD, Leiden University Medical Center Identifier: NCT02387151    
Other Study ID Numbers: NL4724400013
2013-005407-14 ( EudraCT Number )
First Posted: March 12, 2015    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: June 2019
Keywords provided by M.E. J. Reinders, Leiden University Medical Center:
Mesenchymal Stromal Cells