Prebiotic Therapy for Kidney Transplant Outcomes

Overseen By Jeremy P Burton, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Must not be taking: Probiotics, Prebiotics

Disqualifiers: Under 18, Carcinomas, Bowel surgery, Crohn's, others

Compensation: Varies

Number of Visits: 14

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special sugar in human milk, called Human Milk Oligosaccharide (HMO), can benefit individuals who have recently received a kidney transplant. Researchers seek to understand if HMO can enhance kidney function and reduce side effects from transplant medications. Participants will take either HMO or a placebo (a dummy treatment) for about three months, with monitoring to compare results. This trial targets adults undergoing a kidney transplant who have not recently used probiotics or prebiotics. As an Early Phase 1 trial, this research focuses on understanding HMO's effects in people, offering participants the opportunity to be among the first to receive this novel treatment.

Do I need to stop taking my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude those using probiotics or other prebiotics.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Human Milk Oligosaccharides (HMO), the treatment being tested, are generally safe and well-tolerated. Studies have found that adding HMOs to baby formula does not cause harmful effects and supports normal growth. This suggests that HMOs are likely safe for people. The FDA also considers one of the main components of HMO safe, as it naturally occurs in human breast milk.

In summary, the available evidence suggests HMOs are safe for humans. However, since this is an early-stage study, the researchers are still exploring the treatment's safety for kidney transplant patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for improving kidney transplant outcomes, which often focuses on immunosuppressive drugs to prevent rejection, Human Milk Oligosaccharides (HMOs) offer a novel approach by targeting the gut-kidney axis. Researchers are excited because HMOs are unique sugars that help produce short chain fatty acids, especially propionate, which is known to combat issues like hypertrophy, fibrosis, and hypertension. This mechanism not only supports kidney function but also enhances overall vascular health, presenting a potentially groundbreaking method to improve transplant success rates.

What evidence suggests that this trial's treatments could be effective for improving kidney transplant outcomes?

This trial will compare Human Milk Oligosaccharides (HMO) with a placebo to evaluate their effects on kidney transplant outcomes. Research has shown that certain components in human milk, called human milk oligosaccharides (HMOs), can help produce substances like propionate. Propionate may lower the risk of heart problems and high blood pressure. These benefits relate to the "gut-kidney axis," indicating that a healthy gut can positively affect kidney health. Although this research remains in the early stages, it suggests that HMOs might help kidney transplant patients by potentially reducing complications such as delayed graft function. ^{1 2 3 4 6}

Who Is on the Research Team?

Alp Sener, MD

Principal Investigator

London Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are receiving a kidney transplant. It's not suitable for those under 18, unable to consent, with recent carcinomas, using other prebiotics or probiotics, or with a history of bowel surgery and conditions like Crohn's disease.

Inclusion Criteria

I am 18 or older and am receiving a kidney transplant.

Exclusion Criteria

I have had cancer within the last 5 years.

I have a history of Crohn's disease or similar conditions.

I have had surgery on my intestines before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either HMO prebiotic or placebo for 12 weeks to test its effect on renal transplant outcomes

12 weeks

8 visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of graft function and microbiome changes

12 weeks

6 visits (in-person or virtual)

Long-term follow-up

Participants continue to be monitored for adverse events and graft function

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Human Milk Oligosaccharides (HMO)
• Placebo

Trial Overview The study tests if Human Milk Oligosaccharides (HMO), a type of prebiotic, can improve kidney transplant outcomes compared to a placebo. Participants will be randomly assigned to receive either HMO or placebo in double-blind fashion for 12 weeks.

How Is the Trial Designed?

Group I: Human Milk Oligosaccharide (HMO) Active Control 1 Intervention

10 g sachet, self-administered for 3 months. 2'-O-fucosyllactose and lacto-N-neotetraose, novel human milk oligosaccharide (HMO) sugars have been shown to stimulate the production of short chain fatty acids, especially propionate. Propionate has been shown to be important in attenuating hypertrophy, fibrosis, vascular dysfunction and hypertension (Bartolomaeus H et al 2019Mar12) and extremely important for the gut kidney axis (Li L et al 2017Dec11).

Group II: Placebo Placebo Group 1 Intervention

10 g sachet, self-administered for 3 months. Placebo sachets are identical to the HMO sachets in color, taste, smell, size and shape

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

The W. Garfield Weston Foundation

Collaborator

Trials

4

Recruited

210+

St. Joseph's Health Care London

Collaborator

Trials

28

Recruited

2,500+

London Health Sciences Centre

Collaborator

Trials

151

Recruited

60,400+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6164445/

Human Milk Oligosaccharides: 2′-Fucosyllactose (2′-FL) ... The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04428190

Prebiotic Therapy to Improve Outcomes of Renal Transplant Participants will be treated with human milk oligosaccharide (HMO) prebiotic versus placebo over 12 weeks from start of the investigational medication date ( ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2667160324000243

Recent advances in the science of human milk ... We review basic HMO information, including their chemical structures and concentrations, attempts to synthesize HMOs at small and plant scale, studies that ...

4. fda.gov fda.gov/files/food/published/GRAS-Notice-GRN-749-Part-1.pdf

GRAS notice 749 for 2'-O-fucosyllactose 2 INTRODUCTION. 2'-fucosyllactose (2'-FL) is one oligosaccharide in the group of Human Milk. Oligosaccharides (HMO). 2.1 Reason for study. This is a stability ...

5. nestlenutrition-institute.org nestlenutrition-institute.org/publications/human-milk-oligosaccharides-2-fucosyllactose-2-fl-and-lacto-n-neotetraose-lnnt-infant-formula

Human Milk Oligosaccharides: 2'-Fucosyllactose (2'-FL) and ... HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut ...

6. nature.com nature.com/articles/s41598-023-41040-5

Human milk oligosaccharides modulate the intestinal ... Human milk contains over 200 distinct oligosaccharides, which are critical to shaping the developing neonatal gut microbiome.