RejectionPhase 1NeptuneNCT02387151
Allogeneic Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients
A Phase 1 study testing mesenchymal stromal cells in people with Rejection and Graft Loss, run by Leiden University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rejection, Graft Loss
- 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
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2015to Nov 2018
- Phase
- Phase 1
- 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 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients
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.
Read the 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.
- Conditions
- Rejection, Graft Loss
- Being tested
- mesenchymal stromal cells
- Keywords
- Mesenchymal Stromal Cells, Rejection
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mesenchymal stromal cellsDrug
Also called MSC, bone marrow derived 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
| Study group | Role | What they receive |
|---|---|---|
| mesenchymal stromal cells | Experimental | allogeneic mesenchymal stromal cell infusion Receives: Drug: mesenchymal stromal cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
biopsy proven acute rejection / graft loss
Measured: 12 months after transplantation
Secondary outcomes (5)
Comparison of fibrosis by quantitative Sirius Red scoring
Measured: Before MSC infusion (week 24 after transplantation) and 6 months after MSC infusion (week 52 after transplantation)
Serious adverse events
Measured: 12 months after transplantation
Renal function measured by cGFR (MDRD formula) and iohexol clearance
Measured: 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
Measured: from baseline up to 26 weeks after MSC treatment
Development of de novo donor specific antibodies (DSA) and immunological responses
Measured: at baseline, week 24 after transplantation (before MSC treatment) up to week 26 after MSC treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionNov 2018
- Study completionNov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for RejectionStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 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
- NCT02387151
- Sponsor's protocol ID
- NL4724400013
- Other IDs
- 2013-005407-14
- Acronym
- Neptune
- Status last verified
- Jun 2019
- First submitted
- 3 Mar 2015
- Last updated
- 2 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 26537851
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients
- ClinicalTrials.gov ID
- NCT02387151
- Acronym / sponsor ID
- Neptune / NL4724400013
- Conditions
- Rejection, Graft Loss
- Keywords
- Mesenchymal Stromal Cells, Rejection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Mar 2015 (actual)
- Primary completion
- Nov 2018 (actual)
- Study completion
- Nov 2018 (actual)
- First posted
- 12 Mar 2015 (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 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| mesenchymal stromal cells | Experimental | Drug: mesenchymal stromal cellsallogeneic mesenchymal stromal cell infusion |
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 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.
Key exclusion criteria (13 listed)
- 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.
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: MSC, bone marrow derived mesenchymal stromal cells2 doses of 1-2x10^6 allogeneic bone marrow derives MSCs IV per/kg body weight at weeks 25 and 26 after transplantation | Drug | mesenchymal stromal cells |
Primary outcome
biopsy proven acute rejection / graft loss
Time frame: 12 months after transplantation
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2019.
- Derived from this study: PubMed 26537851Reinders 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.
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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 1 study testing mesenchymal stromal cells in people with Rejection and Graft Loss, 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 13 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: finished, as of the sponsor's last update on 2 Jul 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
biopsy proven acute rejection / graft loss (time frame: 12 months after transplantation). 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 NCT02387151, which also lists 1 linked publication.
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 2 Jul 2019.