NCT02711826

Treg Therapy in Subclinical Inflammation in Kidney Transplantation

Treg Adoptive Therapy in Subclinical Inflammation in Kidney Transplantation (CTOT-21)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is: * To see if polyTregs can reduce inflammation in a transplanted kidney. * To find out what effects, good or bad, polyTregs will have in the kidney recipient. * To find out what effects, good or bad, taking everolimus after polyTregs will have in the kidney recipient.

Detailed description

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). PolyTregs, when given to the recipient, might reduce inflammation in the transplanted kidney. However, this effect has not yet been shown. 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 in renal transplant recipients with subclinical inflammation (SCI) in the 3 to 7 months 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.

Conditions

• Kidney Transplant
• Adult Living Donor Kidney Transplant Recipients
• Renal Transplant
• Living Kidney Donor

Interventions

Type	Name	Description
BIOLOGICAL	Polyclonal Regulatory T Cells	Participants randomized to polyTregs group will receive a single infusion of 550 ± 450 x 10\^6 polyTregs.
DRUG	Everolimus
DRUG	Tacrolimus
DRUG	Mycophenolate mofetil	All enrolled participants will be on MMF (or MPA below) at the time of study entry at a minimum dose of 1000mg per day.
DRUG	Mycophenolic acid	All enrolled participants will be on MPA (or MMF above) at the time of study entry at a minimum dose of 720mg per day.
DRUG	Acetaminophen	650 mg acetaminophen, administered 30-60 minutes prior to infusion as pre-medication.
DRUG	Diphenhydramine	25-50 mg diphenhydramine intravenously or by mouth, administered 30-60 minutes prior to infusion as pre-medication.
PROCEDURE	Biopsy, Kidney
PROCEDURE	Blood Draw
PROCEDURE	Leukapheresis
PROCEDURE	IS regimen conversion	Conversion from Tacrolimus, a calcineurin inhibitors (CNI), to Everolimus, an mTOR inhibitor.

Timeline

• Start date: 2016-09-20
• Primary completion: 2023-08-04
• Completion: 2023-08-04
• First posted: 2016-03-17
• Last updated: 2025-04-09
• Results posted: 2024-10-08

Locations

6 sites across 1 country: United States