Prebiotic Therapy to Improve Outcomes of Renal Transplant

October 30, 2023 updated by: Lawson Health Research Institute
An investigator initiated pilot study: two arm, double blind, placebo controlled, randomized, group of approximately 60 patients undergoing a kidney transplant. Participants will be treated with human milk oligosaccharide (HMO) prebiotic versus placebo over 12 weeks from start of the investigational medication date (approximately 3 months) to test whether HMO can improve renal transplant outcomes. Participants will be followed up for 3 months after after they complete the treatment portion of the study. HMO sachets will be administered to determine the safety and efficacy of HMO relative to placebo in improving renal transplant outcomes in patients by reducing delayed graft function and side effects from post transplant therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Nearly three million people worldwide suffer from end stage renal disease (ESRD), which has debilitating consequences on the quality of life of patients There is a discrepancy between the availability of organs and the increasing number of patients placed on the waiting list. Canadians with ESRD requiring kidney transplantation has increased by 38% from 2005-2014, whereas the number of transplantable organs has not met this growing need.

As clinicians use more marginal donors, the effects of ischemic injury from the procurement process become more pronounced. This ischemia reperfusion injury (IRI) has been linked to increased delayed graft function, rejection and decreased long-term function. Approximately 20% of transplanted patients subsequently return to dialysis due to poor graft function. Therefore, one of the major goals of the transplant community has now shifted to ensuring the longevity of transplanted organs. Research priorities need to shift towards developing ways to ensure the longevity of grafts through modification of recipient factors.

Patients are also required to remain on immunosuppressive drugs following transplant in order to maintain the graft. These have a variety of side effects, including diarrhea and intestinal malabsorption, which can lead to a lack of patient compliance with post transplant therapy and a reduced quality of life.

Patients with ESRD also have an expansion of bacteria that produce urease and uric acid and produce fewer short-chained fatty acids and vitamins.

This is important as it is theorized that the production of short-chained fatty acids by microorganisms in the GI tract are crucial as both the energy source, and to the maintenance of intestinal permeability, which contribute to a healthy gastrointestinal tract.

The expansion of bacteria that produce urease and uric acid contribute to toxicity and inflammation in the GI tract that can cause complications in these patients.

In order to reduce both delayed graft function and side effects from post transplant therapy, novel support options are required. One option is the use of prebiotics.

Non-digestible sugar prebiotics have potential for use in these patients. The Principal Investigator/Sponsor will test this potential in a pilot clinical study with a Human milk oligosaccharides (HMO) prebiotic mix that 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 and is extremely important for the gut kidney axis. Prebiotics offer a safe and well-tolerated therapy, which could have a positive impact by improving systemic inflammatory responses, improving gut barrier function, helping to reduce immunosuppressive drug side effects and stabilizing its dosing.

This study will assess blood, and urine samples collected as part of the participant's post-transplant follow up at eight time points to determine graft function.

Urine and a faecal sample will be collected at 6 time points for microbiome analyses at baseline, day 7, 30, 60, 120 and 180 from the date of starting the study product. Prior to commencing their treatment, and at days 60,90,150, and 180, the research coordinator (blinded to the randomisation) will assess patients using the SF-36 and GI Health questionnaires during clinic visits, or by telephone interview.

Protocol compliance will be tested through product count and interviews at each follow-up visit. Side effects will be assessed using standardized case report forms at each visit. Participants will be encouraged to report any events they may experience directly to the coordinator.

Participants who withdraw consent to continue treatments, will be encouraged to undergo the planned assessments. Withdrawal at the request of investigators or medical personnel may include, but are not limited to:

  1. Symptoms are deemed to be potentially related to the study product
  2. New diagnosis of exclusion criteria;
  3. Unacceptable side effects;
  4. Death

Estimated time to complete recruitment: Averaging 86 weeks, approximately 20 months

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • Recruiting
        • London Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Alp Sener, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 years of age and over receiving a kidney transplant.

Exclusion Criteria:

  • Under 18 years of age
  • Inability to give consent
  • Usage of probiotics or other prebiotics.
  • Have had carcinomas during the last 5 years
  • Bowel surgery
  • Crohn ́s disease and other conditions.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo

10 g sachet, self-administered for 3 months.

Placebo sachets are identical to the HMO sachets in color, taste, smell, size and shape
Other: Placebo
Sachet manufactured to mimic 10g of HMO
Other Names:
  • Placebo for HMO
Active Comparator: Human Milk Oligosaccharide (HMO)

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).
Dietary supplement: Human Milk Oligosaccharides (HMO)
Sachet containing 10 grams of HMO
Other Names:
  • Prebiotic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Short Form Health Survey (SF-36)
Time Frame: 24 weeks
The Short Form Health Survey will measure participant satisfaction using a scale from 1 - 5, 1 being the best outcome, and 5 being the worst outcome.
24 weeks
Adverse Events
Time Frame: 24 weeks
Adverse events will be recorded through case report forms and reported to the principal investigator. Side effects will be assessed using standardized case report forms at each visit. Participants are encouraged to contact the coordinator to report any concerns.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microbiome changes from baseline to end of treatment
Time Frame: 12 weeks
Changes in the entire bacterial community from baseline to end of study will be assessed in the lab from faecal and urine samples collected by the participant. The microbes may vary by participant and the study will be looking at which ones present themselves in each case. Units of measure via culture are colony forming units per g (cfu/g).
12 weeks
Microbiome changes post intervention
Time Frame: 12 weeks
Changes in the entire bacterial community after study intervention will be assessed in the lab from faecal and urine samples collected by the participant. The microbes may vary by participant and this outcome measure will be looking at which ones present themselves in each case.
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who experience kidney rejection
Time Frame: 24 weeks
A kidney rejection will be recorded in the adverse event form for the study.
24 weeks
Immunosuppression suppressive drug dose
Time Frame: post-operative day 1, 7, 30, 60, 90, 120, 150 and 180
will be assessed by the clinic on post-operative day 1, 7, 30, 60, 90, 120, 150 and 180
post-operative day 1, 7, 30, 60, 90, 120, 150 and 180
Infectious complications
Time Frame: post-operative day 30, 60, 90, 120, 150 and 180.
Cytomegalovirus will be tested by the clinic, typically reported in IU/mL
post-operative day 30, 60, 90, 120, 150 and 180.
Serum creatinine
Time Frame: 24 weeks.
Will be used to determine graft function, and is reported in μmol/L.
24 weeks.
Cystatin-c levels
Time Frame: 24 weeks.
Will be used to determine graft function, and is reported in mg/l.
24 weeks.
Estimated glomerular filtration rate (eGFR)
Time Frame: 24 weeks.
Will be used to determine graft function, and is reported in mL/min/1.73m**2.
24 weeks.
Urine output
Time Frame: 24 weeks.
Will be used to determine graft function, and is reported in mL/day.
24 weeks.
Urine protein/creatinine ratio
Time Frame: 24 weeks.
Will be used to determine graft function, and is reported in g/L
24 weeks.
Dialysis episodes
Time Frame: 24 weeks.
Will be used to determine graft function, and will be measured by the amount of times a participant required dialysis.
24 weeks.
Renal micro-perfusion using Doppler ultrasound
Time Frame: 24 weeks.
Will be used to determine graft function by providing an assessment of vascular changes.
24 weeks.
Search Results Web results Kidney Injury Molecule-1 (Kim-1)
Time Frame: 24 weeks.
Will be used to determine graft function, and is reported in ng/ml
24 weeks.
Neutrophil gelatinase-associated lipocalin (NGAL)
Time Frame: 24 weeks.
Will be used to determine graft function, and is reported in ng/ml
24 weeks.
Immunosuppression drug serum levels (MMF and FK-506)
Time Frame: post-operative day 1, 7, 30, 60, 90, 120, 150 and 180
will be assessed by the clinic, typically reported in mg/ml.
post-operative day 1, 7, 30, 60, 90, 120, 150 and 180
Serial viral serologies
Time Frame: post-operative day 30, 60, 90, 120, 150 and 180.
Polyomavirus will be tested by the clinic post-op, typically reported in IU/mL.
post-operative day 30, 60, 90, 120, 150 and 180.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Collaborators

London Health Sciences Centre
St. Joseph's Health Care London
The W. Garfield Weston Foundation

Investigators

  • Principal Investigator: Alp Sener, MD, London Health Sciences Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 23, 2022

Primary Completion (Estimated)

October 15, 2024

Study Completion (Estimated)

December 15, 2024

Study Registration Dates

First Submitted

May 28, 2020

First Submitted That Met QC Criteria

June 9, 2020

First Posted (Actual)

June 11, 2020

Study Record Updates

Last Update Posted (Actual)

November 1, 2023

Last Update Submitted That Met QC Criteria

October 30, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • PRT01

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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