Mesenchymal Stromal Cells in Living Donor Kidney Transplantation
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|ClinicalTrials.gov Identifier: NCT03478215|
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : September 17, 2018
|Condition or disease||Intervention/treatment||Phase|
|Renal Transplantation Mesenchymal Stem Cells||Biological: Mesenchymal Stromal Stem Cells (MSCs) Infusion Other: Normal Saline (Placebo) Infusion||Phase 2|
The study is a double-blind, randomized, controlled, dose-escalation and safety study of the investigational product, autologous MSCs, to be assessed for inducing immune suppression in living donor kidney transplant recipients as compared to saline, the placebo infusion. The investigator will obtain exploratory immune response markers to estimate the effect of autologous MSCs on the T- and B-cell response following living donor kidney transplantation. The usual routine care supportive drugs will be given to all: corticosteroids during induction, the calcineurin inhibitor tacrolimus (Prograf®, Astellas Pharma), and mycophenolate mofetil (Cellcept®, Genentech) for maintenance therapy. All subjects will receive basiliximab (Simulect®, Novartis), a standard drug used to induce immune suppression.
Up to 24 patients will be enrolled at the Houston Methodist Hospital. Safety analyses will be conducted after the first 4 subjects have been enrolled and completed the first 30-90 days posttransplant, with subject 2 enrolled 30 days after subject 1 and subject 3 enrolled 30 days after subject 2 (eg, a 30-day window between subject enrollment days). If no safety signal has been detected, the next group of 4 subjects will be enrolled using no less than a 2-week enrollment window from subject 5, 2 weeks from subject 6, and so on. Subjects will be evaluated in the same manner until 8 subjects in the final dosing group have completed 90 days or a decision to stop the study has occurred, whichever comes first. Each subsequent dosing group will begin with a 30-day window of evaluation between subjects enrolled for the first 4 subjects enrolled in the group. If no adverse safety signal has been detected in the first 4 cases in that dosing group, the next 4 subjects enrolled will have a 2-week evaluation window between enrollments. This early evaluation approach will allow for the assessment of the inflammatory period occurring after transplantation. A final safety review will occur at the end of the study and a report will be written.
The study will provide information needed to select a MSC dose level to be used in subsequent clinical trials and to inform the design of subsequent trials.
|Study Type :||Interventional|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||A Double-blind, Randomized, Controlled Dose Escalation Trial of Autologuous Mesenchymal Stromal Cells in Living Donor Kidney Transplant Recipients|
|Study Start Date :||February 2016|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2021|
Experimental: Mesenchymal Stromal Stem Cells Infusion
Intervention: Mesenchymal stromal stem cells infusion. This is the active investigational intervention, administered intravenously at surgery and day 4 post-transplant in a dose-escalation fashion beginning as 1x10^6 cells for the first dose group, 2x10^6 cells for the second dose group, or 3x10^6 cells for the last dose group. The infusion set-up will be covered to mask the group assignment.
Participants will also receive BASILIXIMAB (Simulect, for all subjects at a standard dose, 20mg reconstituted with normal saline or 5% dextrose) on the day of surgery and day 3 or 4 post-transplant administered by a member of the anesthesia team; TACROLIMUS (Prograf for maintenance therapy), MYCOPHENOLATE MOFETIL (Cellcept for maintenance therapy), and CORTICOSTEROIDS as routine care.
Biological: Mesenchymal Stromal Stem Cells (MSCs) Infusion
Investigational infusion bag containing autologous mesenchymal stromal cells wrapped to cover contents to maintain the blind.
Mesenchymal Stromal Stem Cells Infusion.
Other Name: Investigational autologous biological product
Placebo Comparator: Placebo Infusion
Placebo: A normal saline infusion. This is the placebo intervention to occur at surgery and day 4 post-transplant. The infusion set-up will be covered to mask the group assignment. Participants will also receive BASILIXIMAB (Simulect, for all subjects at a standard dose, 20mg reconstituted with normal saline or 5% dextrose) on the day of surgery and day 3 or 4 post-transplant administered by a member of the anesthesia team; TACROLIMUS (Prograf for maintenance therapy), MYCOPHENOLATE MOFETIL (Cellcept for maintenance therapy), and CORTICOSTEROIDS as routine care.
Other: Normal Saline (Placebo) Infusion
Matching infusion containing normal saline wrapped to cover contents to maintain the blind.
Normal Saline (Placebo) Infusion.
Other Name: Matching placebo infusion bag
- Number of participants without any infusional toxicity, occurring within 24 hours of infusion. [ Time Frame: 24 hours from end of infusion ]Infusional toxicity will be assessed as the occurrence of either 1) two or more participants having deep vein thrombosis (Grade 2 thrombotic event); 2) any participant having evidence of the first-pass phenomenon of cells trapping in the lung as evidenced by (a) shortness of breath at rest, (b) requiring ventilator support, or (c) pulmonary edema with hypoxia requiring support; or 3) Grade 4 hypertension or hypotension; or 4) acute myocardial infarction; or 5) new onset congestive heart failure; or 6) capillary leak syndrome; or 7) acute kidney injury; or 8) biopsy-proven rejection.
- Number of participants without any acute rejection, graft loss, or death at 6 months post transplant. [ Time Frame: 6 months post transplant ]Rejection will be determined as biopsy-proven allograft rejection (BPAR). Graft loss will be counted when the patient loses kidney function to the point that they require chronic renal replacement therapy (e.g., dialysis for more than 8 weeks or a re-transplant).
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): NCT03478215
|Contact: Darrel Cleere, BSN,RN,CCRPemail@example.com|
|Contact: Linda W Moore, MS,RDN,LDfirstname.lastname@example.org|
|United States, Texas|
|Houston Methodist Hospital System||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: LaTisha Hargrove 713-441-6013 email@example.com|
|Contact: Darrel Cleere, RN,CCRP 713-441-6232 DWCLEERE@houstonmethodist.org|
|Principal Investigator: Ahmed O Gaber, MD|
|Principal Investigator:||Ahmed O Gaber, MD||Houston Methodist Physicians Organization|