Mesenchymal Stromal Cell Therapy in Renal Recipients (MSCs)
|
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02057965 |
|
Recruitment Status :
Recruiting
First Posted : February 7, 2014
Last Update Posted : March 16, 2018
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Renal Transplant Rejection Fibrosis | Drug: Mesenchymal Stromal Cells | Phase 2 |
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 At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus will be halved, after 2 weeks stopped).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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 70 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Autologous Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Combination With Everolimus to Preserve Renal Structure and Function in Renal Recipients |
| Study Start Date : | March 2014 |
| Estimated Primary Completion Date : | December 2018 |
| Estimated Study Completion Date : | December 2018 |
| Arm | Intervention/treatment |
|---|---|
|
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) |
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 |
|
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).
|
- Fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups [ Time Frame: at 6 months compared to 4 weeks post transplant ]
- 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 ]
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.
| 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 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).
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 ClinicalTrials.gov identifier (NCT number): NCT02057965
| Contact: Marlies EJ Reinders, MD/PhD | m.e.j.reinders@lumc.nl |
| Netherlands | |
| Leiden University Medical Center | Recruiting |
| Leiden, Netherlands, 2333 ZA | |
| Principal Investigator: Marlies EJ Reinders, MD/PhD | |
| Principal Investigator: | Marlies EJ Reinders, MD/PhD | Leiden University Medical Center |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | M.E. J. Reinders, MD/PhD, Leiden University Medical Center |
| ClinicalTrials.gov Identifier: | NCT02057965 History of Changes |
| Other Study ID Numbers: |
NL43712.000.13 2013-000819-25 ( EudraCT Number ) |
| First Posted: | February 7, 2014 Key Record Dates |
| Last Update Posted: | March 16, 2018 |
| Last Verified: | March 2018 |
Keywords provided by M.E. J. Reinders, Leiden University Medical Center:
|
Mesenchymal Stromal Cells Allograft rejection Fibrosis |
Additional relevant MeSH terms:
|
Fibrosis Pathologic Processes Tacrolimus Everolimus Sirolimus Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
Calcineurin Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents |