Renal Transplant RejectionPhase 2MSCsNCT02057965
Mesenchymal Stromal Cell Therapy in Renal Recipients
A Phase 2 study testing Mesenchymal Stromal Cells in people with Renal Transplant Rejection and Fibrosis, run by Leiden University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Renal Transplant Rejection, Fibrosis
- What is being tested?
- Mesenchymal Stromal Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2014to Jan 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Autologous Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Combination With Everolimus to Preserve Renal Structure and Function in Renal Recipients
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.
Read the 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.
- Conditions
- Renal Transplant Rejection, Fibrosis
- Being tested
- Mesenchymal Stromal Cells
- Keywords
- Mesenchymal Stromal Cells, Allograft rejection, Fibrosis
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal Stromal CellsDrug
Also called Bone marrow derived 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
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal Stromal Cells + Everolimus | Active comparator | 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) Receives: Drug: Mesenchymal Stromal Cells |
| Everolimus + Tacrolimus | No intervention | 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups
Measured: at 6 months compared to 4 weeks post transplant
Secondary outcomes (6)
Renal function and proteinuria
Measured: 6 months
Number of participants with CMV and BK infection an other opportunistic infections between groups
Measured: 6 months
Number of participants with adverse events
Measured: 6 months
composite end point efficacy failure (biopsy proven acute rejection, graft loss or death)
Measured: 6 months
Presence of donor specific antibodies and immunologic monitoring
Measured: 6 months
Progression of subclinical cardiovascular disease in the different treatment groups bij assessing echocardiographic parameters
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2014 (estimated)
- Study startMar 2014
- Primary completionJan 2020
- Study completionJan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M.E. J. Reinders, Leiden University Medical Center
- Investigators
- Marlies EJ Reinders, MD/PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02057965
- Sponsor's protocol ID
- NL43712.000.13
- Other IDs
- 2013-000819-25
- Acronym
- MSCs
- Status last verified
- Sep 2020
- First submitted
- 5 Feb 2014
- Last updated
- 17 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Reinders ME, de Fijter JW, Roelofs H, Bajema IM, de Vries DK, Schaapherder AF, Claas FH, van Miert PP, Roelen DL, van Kooten C, Fibbe WE, Rabelink TJ. Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med. 2013 Feb;2(2):107-11. doi: 10.5966/sctm.2012-0114. Epub 2013 Jan 24.
PubMed 23349326van Vugt LK, Zwart TC, Bezstarosti S, Heidt S, Reinders MEJ, Hesselink DA, de Vries APJ, de Winter BCM, Moes DJAR. Alemtuzumab Exposure and T Lymphocyte Depletion: A Population Pharmacokinetic-Pharmacodynamic Model of Alemtuzumab Induction Therapy for Kidney Transplantation. Clin Pharmacol Ther. 2025 Sep;118(3):662-672. doi: 10.1002/cpt.3714. Epub 2025 May 15.
PubMed 40374867Hendriks SH, Heidt S, Schulz AR, de Fijter JW, Reinders MEJ, Koning F, van Kooten C. Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients. Transpl Int. 2023 Jun 23;36:11329. doi: 10.3389/ti.2023.11329. eCollection 2023.
PubMed 37426430Reinders ME, Bank JR, Dreyer GJ, Roelofs H, Heidt S, Roelen DL, Al Huurman V, Lindeman J, van Kooten C, Claas FH, Fibbe WE, Rabelink TJ, de Fijter JW. Autologous bone marrow derived mesenchymal stromal cell therapy in combination with everolimus to preserve renal structure and function in renal transplant recipients. J Transl Med. 2014 Dec 10;12:331. doi: 10.1186/s12967-014-0331-x.
PubMed 25491391
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Combination With Everolimus to Preserve Renal Structure and Function in Renal Recipients
- ClinicalTrials.gov ID
- NCT02057965
- Acronym / sponsor ID
- MSCs / NL43712.000.13
- Conditions
- Renal Transplant Rejection, Fibrosis
- Keywords
- Mesenchymal Stromal Cells, Allograft rejection, Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Jan 2020 (actual)
- Study completion
- Jan 2022 (estimated)
- First posted
- 7 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal Stromal Cells + Everolimus | Active comparator | Drug: Mesenchymal Stromal CellsIntervention: 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) |
| Everolimus + Tacrolimus | No intervention | –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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal Stromal CellsAlso: Bone marrow derived mesenchymal stromal cellsTwo 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 | Drug | Mesenchymal Stromal Cells + Everolimus |
Primary outcome
Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups
Time frame: at 6 months compared to 4 weeks post transplant
6 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2020.
- Results publication: PubMed 23349326Reinders ME, de Fijter JW, Roelofs H, Bajema IM, de Vries DK, Schaapherder AF, Claas FH, van Miert PP, Roelen DL, van Kooten C, Fibbe WE, Rabelink TJ. Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med. 2013 Feb;2(2):107-11. doi: 10.5966/sctm.2012-0114. Epub 2013 Jan 24.
- Derived from this study: PubMed 40374867van Vugt LK, Zwart TC, Bezstarosti S, Heidt S, Reinders MEJ, Hesselink DA, de Vries APJ, de Winter BCM, Moes DJAR. Alemtuzumab Exposure and T Lymphocyte Depletion: A Population Pharmacokinetic-Pharmacodynamic Model of Alemtuzumab Induction Therapy for Kidney Transplantation. Clin Pharmacol Ther. 2025 Sep;118(3):662-672. doi: 10.1002/cpt.3714. Epub 2025 May 15.
- Derived from this study: PubMed 37426430Hendriks SH, Heidt S, Schulz AR, de Fijter JW, Reinders MEJ, Koning F, van Kooten C. Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients. Transpl Int. 2023 Jun 23;36:11329. doi: 10.3389/ti.2023.11329. eCollection 2023.
- Derived from this study: PubMed 25491391Reinders ME, Bank JR, Dreyer GJ, Roelofs H, Heidt S, Roelen DL, Al Huurman V, Lindeman J, van Kooten C, Claas FH, Fibbe WE, Rabelink TJ, de Fijter JW. Autologous bone marrow derived mesenchymal stromal cell therapy in combination with everolimus to preserve renal structure and function in renal transplant recipients. J Transl Med. 2014 Dec 10;12:331. doi: 10.1186/s12967-014-0331-x.
Related trials for Renal Transplant Rejection
Not yet recruitingObservational study
Microbiota Changes Related to Outcomes in Kidney Transplantation
End-stage Renal Disease (ESRD), Kidney Transplantation
RecruitingPhase 1
Treatment of Antibody-Mediated Rejection (ABMR) With CarBel
Kidney Transplant Rejection
RecruitingPhase 2
A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation
Microvascular Inflammation
Recruiting
Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced NK-mediated Rejection
Kidney Transplant Failure and Rejection
Enrolling by invitationObservational study
GEnomic Medicine in Kidney Transplantation Study
Transplant Complication, Kidney Transplant Rejection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marlies EJ Reinders, MD/PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mesenchymal Stromal Cells in people with Renal Transplant Rejection and Fibrosis, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups (time frame: at 6 months compared to 4 weeks post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02057965, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2020.