Clinical trial NCT04428190: Prebiotic Therapy to Improve Outcomes of Renal Transplant
Official title: Prebiotic Therapy to Improve Outcomes of Renal Transplant
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Kidney Transplant; Complications
Keywords: kidney
kidney transplant
prebiotic
human milk oligosaccharide
HMO
renal transplant
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: The W. Garfield Weston Foundation
name: St. Joseph's Health Care London
name: London Health Sciences Centre
First posted: 2020-06-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: One placebo arm and one active treatment arm, participants will be assigned to each arm equally.
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Short Form Health Survey (SF-36)
timeFrame: 24 weeks
measure: Adverse Events
timeFrame: 24 weeks
Secondary outcomes:
measure: Microbiome changes from baseline to end of treatment
timeFrame: 12 weeks
measure: Microbiome changes post intervention
timeFrame: 12 weeks
Other outcomes:
measure: Number of participants who experience kidney rejection
timeFrame: 24 weeks
measure: Immunosuppression suppressive drug dose
timeFrame: post-operative day 1, 7, 30, 60, 90, 120, 150 and 180
measure: Infectious complications
timeFrame: post-operative day 30, 60, 90, 120, 150 and 180.
measure: Serum creatinine
timeFrame: 24 weeks.
measure: Cystatin-c levels
timeFrame: 24 weeks.
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: 24 weeks.
measure: Urine output
timeFrame: 24 weeks.
measure: Urine protein/creatinine ratio
timeFrame: 24 weeks.
measure: Dialysis episodes
timeFrame: 24 weeks.
measure: Renal micro-perfusion using Doppler ultrasound
timeFrame: 24 weeks.
measure: Search Results Web results Kidney Injury Molecule-1 (Kim-1)
timeFrame: 24 weeks.
measure: Neutrophil gelatinase-associated lipocalin (NGAL)
timeFrame: 24 weeks.
measure: Immunosuppression drug serum levels (MMF and FK-506)
timeFrame: post-operative day 1, 7, 30, 60, 90, 120, 150 and 180
measure: Serial viral serologies
timeFrame: post-operative day 30, 60, 90, 120, 150 and 180.
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: London Health Sciences Centre
name: Alp Sener, MD
role: PRINCIPAL_INVESTIGATOR
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