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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.
 
ClinicalTrials.gov Identifier: NCT02387151
Recruitment Status : Completed
First Posted : March 12, 2015
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
M.E. J. Reinders, Leiden University Medical Center

Tracking Information
First Submitted Date  ICMJE March 3, 2015
First Posted Date  ICMJE March 12, 2015
Last Update Posted Date July 2, 2019
Actual Study Start Date  ICMJE March 2015
Actual Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
biopsy proven acute rejection / graft loss [ Time Frame: 12 months after transplantation ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2015)
  • 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) ]
  • Serious adverse events [ Time Frame: 12 months after transplantation ]
  • Renal function measured by cGFR (MDRD formula) and iohexol clearance [ Time Frame: week 24 after transplantation (before MSC infusion) and 52 after transplantation ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients
Official Title  ICMJE Safety of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Rejection
  • Graft Loss
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: mesenchymal stromal cells
allogeneic mesenchymal stromal cell infusion
Intervention: Drug: mesenchymal stromal cells
Publications * Reinders ME, Dreyer GJ, Bank JR, Roelofs H, Heidt S, Roelen DL, Zandvliet ML, Huurman VA, Fibbe WE, van Kooten C, Claas FH, Rabelink TJ, de Fijter JW. Safety of allogeneic bone marrow derived mesenchymal stromal cell therapy in renal transplant recipients: the neptune study. J Transl Med. 2015 Nov 4;13:344. doi: 10.1186/s12967-015-0700-0.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 6, 2015)
10
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2018
Actual Primary Completion Date November 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02387151
Other Study ID Numbers  ICMJE NL4724400013
2013-005407-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party M.E. J. Reinders, Leiden University Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Leiden University Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marlies EJ Reinders, MD/PhD Leiden University Medical Center
PRS Account Leiden University Medical Center
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP