Sucralose as a Way to Enhance Regulatory T Cells, the SWEET Trial: Clinical Research Protocol.

Background: Kidney transplantation is the most effective treatment for patients with end-stage kidney disease. Modern immunosuppressive treatment has prolonged graft survival and reduced transplant rejection. However, these immunosuppressive regimens are associated with multiple side effects, including increased infections and cancer risk, nephrotoxicity, and metabolic complications. Attaining transplant tolerance with minimal reliance on immunosuppressive drugs is considered the ultimate goal in transplantation. Regulatory T cells (Tregs) adoptive immunotherapy has been proposed as a strategy to achieve transplant tolerance. However, this approach is labor-intensive and expensive, limiting its large-scale applicability. There is, therefore, a need to develop methods that promote Treg-mediated tolerance Objective: To determine whether sucralose supplementation increases circulating Treg frequencies and alters T-cell function and populations in healthy adults. Design: This is a randomized, double-blind, placebo-controlled, crossover pilot trial. Setting: The study will be monocentric, at the Maisonneuve-Rosemont Hospital. Patients: Twelve healthy adult volunteers (>18 years of age), of both sexes, with no prior history of autoimmune disease or current treatments of immunomodulatory drugs. In addition, pregnant women will also be excluded from this study. Measurements: The primary outcome will be an alteration in circulating Treg frequency after sucralose supplementation. The secondary outcomes include modulation in the frequency of CD45 Methods: Participants will be randomly assigned to receive either a placebo or sucralose (5-7 mg/kg/day) for four weeks, separated by a two-week washout period. This will be followed by a crossover phase, where patients receiving sucralose will receive the placebo and vice versa for an additional four weeks. Capsules will be prepared and blinded by a licensed pharmacy. Blood will be collected at baseline, after four weeks of treatment or placebo, after washout and after four weeks of crossover for Peripheral Blood Mononuclear Cell (PBMC) isolation, flow cytometry, functional assays, and metabolomics. Stool samples will be collected for microbiome sequencing. Limitations: This will be a small, single-center, short-duration trial in healthy volunteers. Findings might not apply to transplant recipients. Conclusion: The SWEET trial will provide first-in-human data on sucralose as a potential, inexpensive oral immunomodulator to promote Tregs. Trial Registration: NCT06997133 (2025-06-05).