Kidney DiseasesNCT04388930
The Microbiota in Kidney Donation and Transplantation
An observational study of Kidney Diseases and Kidney Transplant Failure and Rejection, run by Royal Free Hospital NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The human gastrointestinal tract harbours ~40 trillion microbial cells, far outnumbering the cell number, and therefore the genetic content of its host. How this genetically diverse bacterial (collectively referred as 'microbiota') co-resident modulates host homeostasis is largely unknown. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Diseases, Kidney Transplant Failure and Rejection, Urinary Tract Infections
- What is being tested?
- Pre-operative assessment - blood, urine, & faecal sample, Post-operative day 3 assessment - blood, urine, & faecal sample and Post-operative week 4-6 assessment - blood, urine, & faecal sample
- How many people
- 130 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2020to 1 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
Study population: Renal transplant live-donors and recipients of live-donor and cadaveric renal transplants
Who may be able to join
- All adult (≥18 years old) undergoing living donor nephrectomy or kidney transplantation. Patients willing to provide samples including Urine, Blood, Faecal samples.
- Participant able to give Informed Consent
- All patients will be at least 18 years old
- Patients will either be a live renal transplant donor or a renal transplant recipient on the waiting list to have or will have had an ABO-blood group compatible renal transplant.
- Patients attending hospital clinics at participating centre for routine clinical follow -up.
- Patients willing to comply with study procedures and willing to provide blood, faecal and urine samples.
Who cannot join
- Patients under the age of 18 years
- Patients unable to give informed consent
- Patients not able to comply with study procedures or follow-up visits
- Patients that are not a live renal donor or that are not on the waiting list to have or have not had an ABO blood group compatible renal transplant and are not attending hospital outpatient clinics at participating study centres for routine clinical follow-up.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Free London NHS Trust
London, NW3 2QG
Reza Motallebzadeh, PhD FRCS, r.motallebzadeh@ucl.ac.uk
Amanda Bidle, 00442077940500 ext. 32535, rf.sponsoredresearch@nhs.net
About this study
Official title: Longitudinal Characterisation of the Host Microbiota After Kidney Donation and Transplantation
The human gastrointestinal tract harbours ~40 trillion microbial cells, far outnumbering the cell number, and therefore the genetic content of its host. How this genetically diverse bacterial (collectively referred as 'microbiota') co-resident modulates host homeostasis is largely unknown. We are increasing gaining a better understanding how the microbes modulate mucosal and systemic metabolic/immune and organ systems including the kidney, heart and the brain. Therapeutic targeting of the gastrointestinal (GI) microbiota may help improve clinical outcomes in conditions as diverse as arthritis, cardiovascular disease, and cancer. In contrast to other organ systems, studies investigating the role of the microbiota in modulating clinical outcomes in renal transplantation lags behind.
The aim of the study is to examine (a) how alterations in the urinary and GI microbiota and associated metabolites impact on host immunity after renal transplantation, and (b) whether such changes are correlated with post-transplant complications, such as rejection, development of de novo donor specific antibodies, metabolic complications (e.g post-transplant diabetes) and infections. Participants will be followed before and up to twelve months post-transplantation, and, longitudinal microbial data will be correlated with in-depth immune phenotyping and clinical end-points to define the impact that changes in urinary and GI microbial ecology have on kidney transplant outcomes.
- Being tested
- Pre-operative assessment - blood, urine, & faecal sample, Post-operative day 3 assessment - blood, urine, & faecal sample, Post-operative week 4-6 assessment - blood, urine, & faecal sample, Post-operative 3 month assessment - blood, urine, & faecal sample, Pre-operative 6 month assessment - blood, urine, & faecal sample
- Medical subject headings
- Kidney Diseases, Rejection, Psychology, Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pre-operative assessment - blood, urine, & faecal sampleOther
Blood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature.
Urine and faecal samples for 16S rRNA gene sequencing
Post-operative day 3 assessment - blood, urine, & faecal sampleOther
Blood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature.
Urine and faecal samples for 16S rRNA gene sequencing.
Post-operative week 4-6 assessment - blood, urine, & faecal sampleOther
Blood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature.
Urine and faecal samples for 16S rRNA gene sequencing.
Post-operative 3 month assessment - blood, urine, & faecal sampleOther
Blood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature.
Urine and faecal samples for 16S rRNA gene sequencing.
Pre-operative 6 month assessment - blood, urine, & faecal sampleOther
Blood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature.
Urine and faecal samples for 16S rRNA gene sequencing.
Post-operative month 12 recipient assessment - blood, urine, & faecal sampleOther
Blood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature.
Urine and faecal samples for 16S rRNA gene sequencing.
| Study group | Role | What they receive |
|---|---|---|
| Kidney transplant live-donor | Participants that will be a planned live renal transplant donor Receives: Other: Pre-operative assessment - blood, urine, & faecal sample; Other: Post-operative day 3 assessment - blood, urine, & faecal sample; Other: Post-operative week 4-6 assessment - blood, urine, & faecal sample; Other: Post-operative 3 month assessment - blood, urine, & faecal sample; Other: Pre-operative 6 month assessment - blood, urine, & faecal sample; Other: Post-operative month 12 recipient assessment - blood, urine, & faecal sample | |
| Kidney transplant recipient | Renal transplant recipient on the waiting list to have or will have had an ABO-blood group compatible live-donor or cadaveric transplant Receives: Other: Pre-operative assessment - blood, urine, & faecal sample; Other: Post-operative week 4-6 assessment - blood, urine, & faecal sample; Other: Post-operative 3 month assessment - blood, urine, & faecal sample; Other: Pre-operative 6 month assessment - blood, urine, & faecal sample; Other: Post-operative month 12 recipient assessment - blood, urine, & faecal sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in gastrointestinal and urinary microbiota composition and diversity
To understand the overall impact of transplantation on changes to the urinary and GI microbiota, the relative abundance of bacterial taxa will be evaluated using 16S rRNA gene sequencing methodologies. Alpha and Beta diversity indices will be determined from urine samples and faecal samples before and after live-donation and transplantation.
Measured: 1 year
Correlation of change in gastrointestinal and urinary microbiota diversity with post-transplantation outcomes.
Incidence of renal graft dysfunction will be determined by the Modification of Diet in Renal Disease (MDRD)-derived estimated Glomerular Filtration Rate (eGFR) at 12 months.
Graft survival time - date of transplantation to date of irreversible graft failure signified by return to dialysis (or re-transplantation, whichever is earlier) or the date of last follow-up during the period when the transplant was still functioning. In the event of death with a functioning graft, the follow-up period will be censored at the date of death.
Measured: 1 year
Secondary outcomes (7)
Change in frequency of conventional and regulatory immune phenotypes and correlation with clinical outcome and microbial diversity changes
A panel of validated immune monitoring assays (including multi-colour flow cytometry, intracellular cytokine staining, enzyme-linked immune absorbent spot [ELISpot], enzyme-linked immunosorbent assay [ELISA] and transcriptional analysis) will be used to analyse immunological parameters in patient samples.
Measured: 1 year
Change in microbial-associated metabolite profile and correlation with clinical outcomes and/or microbial diversity changes
A combination of 1H nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry will be used to measure the metabolic phenotype of urine and faecal samples from transplant donors and recipients (pre-operatively and up to 12 months after surgery).
Measured: 1 year
Incidence of renal graft dysfunction as determined by the MDRD-derived estimated Glomerular Filtration Rate (eGFR).
A significant deterioration in graft dysfunction is defined as the percent of patients exhibiting an eGFR <45 mL/min/1.73m2 at month 12 or a decrease in eGFR ≥10 mL/min/1.73m2 from month 3 to month 12 after transplantation.
Measured: 1 year
The proportion of patients reaching a defined CKD stage at up to 5 years after transplantation.
Defined by the kidney disease outcomes quality initiative for CKD stages, with eGFR <30 mL/min/1.73m2 considered to be advanced renal dysfunction.
Measured: 5 years
Incidence of biopsy proven acute or chronic cellular or humoral rejection up to 5 years after transplantation as per Banff classification
Revised Banff 2017 classification of antibody-mediated rejection and T cell-mediated rejection in renal allografts.
Measured: 5 years
Incidence of post-donation and post-transplant bacterial or viral infections up to 5 years after surgery
Infectious complications will include, but not be limited to, urinary tract infections (defined as a positive urine culture [>50,000 CFUs/ml] from mid-stream urine, and categorised as asymptomatic bacteriuria [no symptoms], cystitis [lower urinary tract symptoms without systemic features] or pyelonephritis [systemic features, graft dysfunction, CRP>50]), BK viraemia, cytomegalovirus (CMV) viraemia, and respiratory tract (RV) infections.
Measured: 5 years
Patient and graft survival rates up to 5 years after transplantation.
Graft survival time will be calculated from the date of transplantation to the date of irreversible graft failure signified by return to dialysis (or re-transplantation, whichever is earlier) or the date of last follow-up during the period when the transplant was still functioning. In the event of death with a functioning graft, the follow-up period will be censored at the date of death.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2020
- Study start1 Mar 2020
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Free Hospital NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London
- Responsible party
- Sponsor
- Investigators
- Research and Development Manager, Study chair, Sponsor GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04388930
- Sponsor's protocol ID
- 125570
- Status last verified
- Dec 2023
- First submitted
- 12 May 2020
- Last updated
- 14 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Characterisation of the Host Microbiota After Kidney Donation and Transplantation
- ClinicalTrials.gov ID
- NCT04388930
- Acronym / sponsor ID
- 125570
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Royal Free Hospital NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University College, London
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 14 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The human gastrointestinal tract harbours ~40 trillion microbial cells, far outnumbering the cell number, and therefore the genetic content of its host. How this genetically diverse bacterial (collectively referred as 'microbiota') co-resident modulates host homeostasis is largely unknown. We are increasing gaining a better understanding how the microbes modulate mucosal and systemic metabolic/immune and organ systems including the kidney, heart and the brain. Therapeutic targeting of the gastrointestinal (GI) microbiota may help improve clinical outcomes in conditions as diverse as arthritis, cardiovascular disease, and cancer. In contrast to other organ systems, studies investigating the role of the microbiota in modulating clinical outcomes in renal transplantation lags behind.
The aim of the study is to examine (a) how alterations in the urinary and GI microbiota and associated metabolites impact on host immunity after renal transplantation, and (b) whether such changes are correlated with post-transplant complications, such as rejection, development of de novo donor specific antibodies, metabolic complications (e.g post-transplant diabetes) and infections. Participants will be followed before and up to twelve months post-transplantation, and, longitudinal microbial data will be correlated with in-depth immune phenotyping and clinical end-points to define the impact that changes in urinary and GI microbial ecology have on kidney transplant outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Kidney transplant live-donor | – | Other: Pre-operative assessment - blood, urine, & faecal sample, Other: Post-operative day 3 assessment - blood, urine, & faecal sample, Other: Post-operative week 4-6 assessment - blood, urine, & faecal sample, Other: Post-operative 3 month assessment - blood, urine, & faecal sample, Other: Pre-operative 6 month assessment - blood, urine, & faecal sample, Other: Post-operative month 12 recipient assessment - blood, urine, & faecal sampleParticipants that will be a planned live renal transplant donor |
| Kidney transplant recipient | – | Other: Pre-operative assessment - blood, urine, & faecal sample, Other: Post-operative week 4-6 assessment - blood, urine, & faecal sample, Other: Post-operative 3 month assessment - blood, urine, & faecal sample, Other: Pre-operative 6 month assessment - blood, urine, & faecal sample, Other: Post-operative month 12 recipient assessment - blood, urine, & faecal sampleRenal transplant recipient on the waiting list to have or will have had an ABO-blood group compatible live-donor or cadaveric transplant |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Renal transplant live-donors and recipients of live-donor and cadaveric renal transplants
Key inclusion criteria (6 listed)
- All adult (≥18 years old) undergoing living donor nephrectomy or kidney transplantation. Patients willing to provide samples including Urine, Blood, Faecal samples.
Key exclusion criteria (4 listed)
- Patients under the age of 18 years
- Patients unable to give informed consent
- Patients not able to comply with study procedures or follow-up visits
- Patients that are not a live renal donor or that are not on the waiting list to have or have not had an ABO blood group compatible renal transplant and are not attending hospital outpatient clinics at participating study centres for routine clinical follow-up.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pre-operative assessment - blood, urine, & faecal sampleBlood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature. Urine and faecal samples for 16S rRNA gene sequencing | Other | Kidney transplant live-donor, Kidney transplant recipient |
| Post-operative day 3 assessment - blood, urine, & faecal sampleBlood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature. Urine and faecal samples for 16S rRNA gene sequencing. | Other | Kidney transplant live-donor |
| Post-operative week 4-6 assessment - blood, urine, & faecal sampleBlood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature. Urine and faecal samples for 16S rRNA gene sequencing. | Other | Kidney transplant live-donor, Kidney transplant recipient |
| Post-operative 3 month assessment - blood, urine, & faecal sampleBlood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature. Urine and faecal samples for 16S rRNA gene sequencing. | Other | Kidney transplant live-donor, Kidney transplant recipient |
| Pre-operative 6 month assessment - blood, urine, & faecal sampleBlood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature. Urine and faecal samples for 16S rRNA gene sequencing. | Other | Kidney transplant live-donor, Kidney transplant recipient |
| Post-operative month 12 recipient assessment - blood, urine, & faecal sampleBlood sample for multi-parametric flow cytometry. Blood and urine samples for identifying microbial-associated metabolite signature. Urine and faecal samples for 16S rRNA gene sequencing. | Other | Kidney transplant live-donor, Kidney transplant recipient |
Primary outcome
Change in gastrointestinal and urinary microbiota composition and diversity
Time frame: 1 year
To understand the overall impact of transplantation on changes to the urinary and GI microbiota, the relative abundance of bacterial taxa will be evaluated using 16S rRNA gene sequencing methodologies. Alpha and Beta diversity indices will be determined from urine samples and faecal samples before and after live-donation and transplantation.
Correlation of change in gastrointestinal and urinary microbiota diversity with post-transplantation outcomes.
Time frame: 1 year
Incidence of renal graft dysfunction will be determined by the Modification of Diet in Renal Disease (MDRD)-derived estimated Glomerular Filtration Rate (eGFR) at 12 months. Graft survival time - date of transplantation to date of irreversible graft failure signified by return to dialysis (or re-transplantation, whichever is earlier) or the date of last follow-up during the period when the transplant was still functioning. In the event of death with a functioning graft, the follow-up period will be censored at the date of death.
7 secondary outcomes
Change in frequency of conventional and regulatory immune phenotypes and correlation with clinical outcome and microbial diversity changes
Time frame: 1 year
Change in microbial-associated metabolite profile and correlation with clinical outcomes and/or microbial diversity changes
Time frame: 1 year
Incidence of renal graft dysfunction as determined by the MDRD-derived estimated Glomerular Filtration Rate (eGFR).
Time frame: 1 year
The proportion of patients reaching a defined CKD stage at up to 5 years after transplantation.
Time frame: 5 years
Incidence of biopsy proven acute or chronic cellular or humoral rejection up to 5 years after transplantation as per Banff classification
Time frame: 5 years
Incidence of post-donation and post-transplant bacterial or viral infections up to 5 years after surgery
Time frame: 5 years
Patient and graft survival rates up to 5 years after transplantation.
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Research and Development Manager study chair
Sponsor GmbH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Diseases and Kidney Transplant Failure and Rejection, run by Royal Free Hospital NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Reza Motallebzadeh (020 7794 0500, r.motallebzadeh@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in gastrointestinal and urinary microbiota composition and diversity (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2023.