The purpose of this study is: - To see if polyTregs and/or "donor reactive" darTregs can reduce inflammation in a transplanted kidney. - To find out what effects, good or bad, polyTregs or darTregs will have in the kidney recipient. - To find out what effects, good or bad, taking everolimus after polyTregs or darTregs will have in the kidney recipient.
Treg Adoptive Therapy in Subclinical Inflammation in Kidney Transplantation (CTOT-21)
Inflammation occurs when the body's defense system recognizes a foreign object (such as a transplanted kidney), and responds by sending white blood cells to attack the foreign object. These cells and the substances they produce can damage the transplanted kidney. There is currently no standard treatment for inflammation in the kidney; some transplant centers do not treat inflammation at all. Rejection is a more severe form of inflammation and injury. Both inflammation and rejection are diagnosed by looking at a piece of kidney (a kidney biopsy) under a microscope. Kidneys that have inflammation and/or rejection do not work as well or last as long as kidneys without injury.
People who have a transplant take immunosuppressive drugs (IS) to prevent inflammation and rejection. Although kidney transplant recipients usually do well in the first five years after transplant, transplant researchers are interested in finding ways to prevent inflammation and rejection without IS, or with lower doses of IS in order to avoid side effects.
While some white blood cells cause inflammation, other types of white blood cells, called T regulatory cells (Tregs), can control inflammation. Tregs may have an important role in controlling or preventing inflammation and rejection. A person's Tregs can be grown in the laboratory to increase their number (polyTreg). These Tregs can be given back through a needle placed in a vein (IV). Researchers can expose a transplant recipient's Tregs to the donor's cells, which results in Tregs that recognize the donor. These are called donor reactive Tregs (darTreg). Both polyTregs and darTreg, when given to the recipient, might reduce inflammation in the transplanted kidney. However, this effect has not yet been shown. The darTregs are thought to be more effective because they might be able to help the body specifically recognize and accept the donated kidney. This is one of the first clinical trials using darTregs.
One of the IS drugs used in kidney transplant is Everolimus. Everolimus has been shown to help Tregs survive better than other types of IS drugs.
This is a randomized open‐label trial to determine the safety and efficacy of a single dose of autologous polyTregs or darTregs in renal transplant recipients with subclinical inflammation (SCI) in the 6 month post‐transplant allograft protocol biopsy compared to control patients treated with CNI‐based immunosuppression. The efficacy of the Treg therapy will be assessed by the reduction of graft inflammation on biopsies performed at 7 months after study group allocation compared to the eligibility biopsy.
Kidney Transplant Adult Living Donor Kidney Transplant Recipients Renal Transplant Living Kidney Donor graft inflammation Treg polyclonally expanded Tregs (polyTregs) darTregs calcineurin inhibitors (CNIs) mTOR inhibitors Everolimus Sirolimus Mycophenolic Acid Tacrolimus Mycophenolate mofetil Calcineurin Inhibitors Diphenhydramine Promethazine Acetaminophen
Open to people ages 18 years and up
Individuals who meet all of the following criteria are eligible for enrollment as study participants:
Treg Infusion Inclusion Criteria:
Individuals randomized to the polyTreg and darTreg groups who continue to meet all of the enrollment criteria.
mTOR Conversion Inclusion Criteria:
Individuals who meet all of these criteria are eligible for mTOR conversion:
Individuals who meet any of these criteria are not eligible for enrollment as study participants:
Treg Infusion Exclusion Criteria:
Individuals randomized to polyTreg and darTreg groups who meet any of these criteria are not eligible for Treg infusion:
Positive pregnancy test for women of child bearing potential.
mTOR Conversion Exclusion Criteria:
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