Sucralose as a Way to Enhance Regulatory T Cells (SWEET)

Sucralose as a Way to Enhance Regulatory T Cells: The Sweet Trial

Title: Taking the SWEET approach to protect the transplanted kidney.

Background: Kidneys are essential organs in our body. When they do not work, patients require machines to help them or receive a new kidney from a donor (transplantation) to survive. Thus far, transplantation is the best treatment. However, the immune system will recognize the new kidney as foreign and try to destroy it, which is called kidney rejection. To prevent rejection, patients with kidney transplants depend on drugs to suppress the immune system. However, these drugs have many side effects, including the risk of infection, cancer, and diabetes.

The immune system is made of many different types of cells. One cell type in particular is T cells that, when kept unchecked, will attack the kidney transplant. However, there is a small subset of these T cells called regulatory T cells (Tregs) that police the immune system and aid in accepting the new kidney. Current ways to increase these police cells (Tregs) after a transplant are expensive and not widely available. Therefore, there is a need to find a better and more accessible way to increase Treg numbers after a transplant to increase the longevity of the newly transplanted kidney.

What we eat is critical in shaping the immune system. Artificial sweeteners, like sucralose (found in Splenda), are often used as a sugar substitute. They are low in calories and safe to consume. However, recent studies suggest they may have unexpected effects on the body. Research in mice has shown that sucralose impacts the immune system. Specifically, the investigators have found that it could suppress T cells that could cause kidney rejection while increasing the Tregs (the police).

Given these findings, the investigators hypothesize that sucralose could be beneficial in conditions where dampening the immune system is desirable, such as in the case of transplantation. By boosting Tregs and reducing the anti-transplant T cells, sucralose may help to protect against organ rejection.

Purpose: The goal of this study is thus to test whether sucralose can safely and effectively modulate the immune system in humans.

Method: The investigator propose to test the impact of sucralose on the immune system. This pilot study will test the effect of sucralose in 10 healthy volunteers. The participants will take sucralose or placebo as a pill twice daily for a month. Healthy volunteers will then stop for a two weeks (washout period). After the washout period, the volunteers on sucralose will switch to placebo, while the placebo group will switch to sucralose pills for one more months. The investigators will take blood samples at the beginning, after one month, after the washout and at the end of the study to study how the immune system changes.

Anticipated outcomes: The investigators expect that sucralose will impact the immune system and increase the number of regulatory T cells.

Relevance to patient/community: Artificial sweeteners are commonly used in the food and pharmaceutical industries. However, their impact on the immune system has not been thoroughly investigated in humans.

Conclusion: Kidney transplantation is the most effective treatment for kidney failure, but the immune system's rejection of the transplanted organ remains a major challenge. Current immunosuppressive drugs used to prevent rejection have significant side effects, underscoring the need for safer alternatives. The investigator research suggests that sucralose, a widely used artificial sweetener, may offer a novel solution by increasing the good T cells (Tregs) and reducing harmful T cells that contribute to rejection. This pilot study will explore sucralose's potential to modulate the immune system in humans, potentially leading to improved transplant outcomes and broader implications for immune regulation.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteer
• Intervention / Treatment: Dietary supplement: sucralose; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caroline Lamarche, MD, MSc; Phone Number: 8682 514-252-3400; Email: caroline.lamarche.1@umontreal.ca
• Study Contact Backup: Name: Julianna Blagih, PhD; Phone Number: 514-252-3400; Email: juliannablagih@gmail.com

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T2M4
      • Centre de recherche de l'Hôpital Maisonneuve-Rosemont
      • Contact: Caroline Lamarche, MD, MSc; Phone Number: 8682 514-252-3400; Email: caroline.lamarche.1@umontreal.ca
      • Principal Investigator: Caroline Lamarche, MD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body weight comparable to average reported in Canada

Exclusion Criteria:

• Past medical history of autoimmune disease
• The use of any regular medication except contraceptive pills
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Starting with placebo - washout - sucralose.; This group will start with a placebo (4 weeks) , then will have a washout period (2 weeks) and then will test sucralose (4 weeks)	Dietary supplement: sucralose; Encapsulated sucralose po BID; Other: Placebo; Encapsulated lactose po bid
Active Comparator: Starting with sucralose - washout - placebo.; This group will start with sucralose (4 weeks) , then will have a washout period (2 weeks) and then will test the placebo (4 weeks)	Dietary supplement: sucralose; Encapsulated sucralose po BID; Other: Placebo; Encapsulated lactose po bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regulatory T cells	Change in % regulatory T cells on total CD4+ T cells compared to baseline	After 4 weeks on sucralose and placebo.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T cell cytokine production (TNFa, IFNy, IL2)	% cytokine production o CD4+ and CD8+ T cells	4 weeks compared to baseline on either placebo or sucralose
Frequency of immune populations in the blood (CD4+, CD8+, NK, B cells, CD11b myeloid cells)	% of CD45+ cells (total immune marker)	4 weeks compared to baseline on either sucralose or placebo
Frequency of CD4+ T cells lineages	% RORyt, T-bet, GATA3 on CD4+ T cells	4 weeks compared to baseline on sucralose or placebo
Frequency of naive, central and effector memory or terminally differentiated CD4+ and CD8+ T cells	% of CD62L+CD45RA+CD45RO- (naive), CD62L+CD45RO+CD44+CD45RA- (central memory), CD62L-CD45RA-CD45RO+CD44+ (effector memory) and CD62L-CD45RA+CD45RO (terminally differentiated cells) on both CD4+ and CD8+ T cells	4 weeks compared to baseline on both sucralose or placebo

Collaborators and Investigators

• Sponsor: Caroline Lamarche
• Collaborators: Ciusss de L'Est de l'Île de Montréal

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: May 21, 2025
• First Posted (Actual): May 30, 2025

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: immune system; regulatory T cells; metabolomic; sucralose
• Other Study ID Numbers: 2025-3912

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No