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Trial record 96 of 1851 for:    "bone marrow" | Recruiting, Not yet recruiting Studies

Mesenchymal Stromal Cell Therapy in Renal Recipients (MSCs)

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ClinicalTrials.gov Identifier: NCT02057965
Recruitment Status : Recruiting
First Posted : February 7, 2014
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
M.E. J. Reinders, Leiden University Medical Center

Tracking Information
First Submitted Date  ICMJE February 5, 2014
First Posted Date  ICMJE February 7, 2014
Last Update Posted Date August 14, 2019
Study Start Date  ICMJE March 2014
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2014)
Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups [ Time Frame: at 6 months compared to 4 weeks post transplant ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02057965 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2014)
  • Renal function and proteinuria [ Time Frame: 6 months ]
  • Number of participants with CMV and BK infection an other opportunistic infections between groups [ Time Frame: 6 months ]
  • Number of participants with adverse events [ Time Frame: 6 months ]
  • composite end point efficacy failure (biopsy proven acute rejection, graft loss or death) [ Time Frame: 6 months ]
  • Presence of donor specific antibodies and immunologic monitoring [ Time Frame: 6 months ]
  • Progression of subclinical cardiovascular disease in the different treatment groups bij assessing echocardiographic parameters [ Time Frame: 6 months ]
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 Mesenchymal Stromal Cell Therapy in Renal Recipients
Official Title  ICMJE Autologous Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Combination With Everolimus to Preserve Renal Structure and Function in Renal Recipients
Brief Summary This study will test the hypothesis that MSCs in combination with Everolimus facilitate Tacrolimus withdrawal, reduce fibrosis and decrease the incidence of opportunistic infections compared to standard tacrolimus dose.
Detailed Description

Kidney transplantation has improved survival and quality of life for patients with end-stage renal disease. Despite excellent short-term results, long-term survival of transplanted kidneys has not improved accordingly in the last decades. Calcineurin inhibitors (CNI) have been the cornerstone of immunosuppressive therapy for many years, due to their efficacy in preventing acute rejection. However, CNI have nephrotoxic side effects that can directly contribute to renal dysfunction and compromise long-term outcomes. Consequently there is a strong interest in immunosuppressive (IS) regimens that maintain efficacy for the prevention of acute rejection, whilst reducing nephrotoxicity.

In this perspective the combination of mesenchymal stromal cells (MSCs) with a mTor inhibitor (Everolimus (Certican®)) might be an optimal strategy to facilitate CNI (tacrolimus) withdrawal. MSCs have IS properties and roles in tissue repair and everolimus is a proliferation signal inhibitor with potent immunosuppressant effects. In experimental studies the combination of mTor inhibitor and MSCs was shown to attenuate alloimmune responses and to promote allograft tolerance.

In total 70 de novo renal recipients, 18-75 years of ages will be recruited from the transplant clinics of the LUMC. Thirty five of these patients will be included in the Certican/ and MSC group and 35 patients in the Certican/ standard dose tacrolimus group. Patients of the MSC treated groups will receive two doses of autologous BM derived MSCs IV, 7 days apart, 6 and 7 weeks after transplantation in combination with Certican® (1.5 mg b.i.d.). At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus will be halved, after 2 weeks stopped). Patients in the control group will receive Certican® (1.5 mg b.i.d.) and standard dose tacrolimus (through levels 6-8 ng/ml after 6 weeks).

Primary goal is evaluate whether concentration-controlled Certican® with MSCs compared to Certican® with standard tacrolimus in renal transplant recipients reduces fibrosis by quantitative Sirius Red scoring.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Renal Transplant Rejection
  • Fibrosis
Intervention  ICMJE Drug: Mesenchymal Stromal Cells
Two doses of autologous bone marrow (BM) derived MSCs IV, 7 days apart, 6 and 7 weeks after transplantation. Doses of MSCs will be 1-2x10^6 million MSCs per/kg body weight
Other Name: Bone marrow derived mesenchymal stromal cells
Study Arms  ICMJE
  • Active Comparator: Mesenchymal Stromal Cells + Everolimus

    Intervention: two doses of autologous bone marrow (BM) derived Mesenchymal Stromal Cells IV, 7 days apart, 6 and 7 weeks after transplantation in combination with Certican® (1.5mg/day). Doses of MSCs will be 1-2x10^6 million MSCs per/kg body weight.

    At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus wil be halved, after 2 weeks stopped)

    Intervention: Drug: Mesenchymal Stromal Cells
  • No Intervention: Everolimus + Tacrolimus
    Patients in the control group will receive Certican® (1.5 mg b.i.d.) and standard dose tacrolimus (through levels 6-8 ng/ml after 6 weeks).
Publications *

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 6, 2014)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date January 2020   (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 deceased, living-unrelated or non-HLA identical living related donor > 50 years of age.
  • Panel Reactive Antibodies (PRA) ≤ 10%.
  • 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 first 6 weeks after transplantation.
  • 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.
  • Patients who have had a previous BM transplant.
  • 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 TB 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 TB, 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).
  • Contraindications to undergo a BM biopsy.
  • Patients who are recipients of ABO incompatible transplants.
  • Cold ischemia time >30 hrs.
  • 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: Marlies EJ Reinders, MD/PhD m.e.j.reinders@lumc.nl
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02057965
Other Study ID Numbers  ICMJE NL43712.000.13
2013-000819-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.E. J. Reinders, Leiden University Medical Center
Study Sponsor  ICMJE Leiden University Medical Center
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 August 2019

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