Renal TransplantCOMET-DRNCT03043339
Characterization Of the Intestinal Microbiome Evolution After Kidney Transplant Donation or Receipt
An observational study of Renal Transplant, run by Emory University at 2 sites in United States.
Trial summary
This is a hypothesis-generating pilot study. The intent is to model the impact of perioperative practices on the intestinal microbiome and possibly associate these conditions with the final microbiome status (e.g., number of resistance genes and diversity associated with perioperative practices and preoperative… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplant
- What is being tested?
- Stool Specimen Collection, Anal Swab Sampling and Short Diet Assessment (SDA)
- How many people
- 3 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Oct 2017to 10 Jan 2019
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Renal transplant recipients and living donors
Who may be able to join
- Ability to understand and the willingness to sign a written informed consent document.
- Ability and willingness to comply with study protocol requirements.
- Completed Verbal Screening Form
- Planned kidney donation or planned receipt of a living donor kidney transplant within 28 days from time of written informed consent.
- If performance status is known, a score of any of the following:
- American Society of Anesthesia (ASA) classification of I (a normal healthy patient), II (a patient with mild systemic disease) or III (a patient with severe systemic disease)
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- Eastern Cooperative Oncology Group (ECOG) Status Scale grade of 0 (normal activity), 1 (symptoms, but ambulatory) or 2 (in bed <50% of the time)
- Karnofsky Performance Scale (KPS) of 50% (requires considerable assistance and frequent medical care) to 100% (normal, no complaints, no evidence of disease)
- English speaking.
Who cannot join
- Any condition that, in the opinion of the investigator, might interfere with study objectives or limit compliance with study requirements, including but not limited to:
- Known active intravenous drug or alcohol abuse
- Psychiatric illness
- Social situation
- Planned or actual receipt of a deceased donor kidney transplant.
- Prior kidney transplant that still requires active immunosuppressive treatment or intervention.
- Presence of diverting ileostomy or colostomy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Emory Clinic
Atlanta, Georgia, 30322
Emory University Hospital
Atlanta, Georgia, 30324
About this study
This is a hypothesis-generating pilot study. The intent is to model the impact of perioperative practices on the intestinal microbiome and possibly associate these conditions with the final microbiome status (e.g., number of resistance genes and diversity associated with perioperative practices and preoperative microbiome status). Participants will include individuals who are having surgery to either receive or donate a kidney. To determine the diversity change of the intestinal microbiota over time, rectal swabs will be collected before surgery and at several time points after surgery, with the last swab collected 30 days after surgery.
This pilot study is to obtain preliminary data to support the rationale and design for a subsequent clinical trial. This study is designed to understand the intestinal microbiota diversity in the setting of renal transplant surgery and the clinical significance of antibiotic use and the associated resistome (collection of all antibiotic resistance genes and precursors within a sample).
Read the detailed description
The emergence of multidrug resistant organisms (MDROs) is a growing threat to global public health and is associated with high morbidity and mortality in both the general and solid organ transplant population. Intestinal microbiota diversity can provide functional and spatial barriers to bacterial and fungal MDRO colonization, and loss of diversity is associated with increased MDRO colonization. Dysbiosis is a state of loss of microbiota diversity and a single antibiotic treatment course can cause significant disruption in microbiota diversity, even in otherwise healthy individuals. This disruption can promote the growth of pathogenic and multidrug-resistant bacteria and fungi. Transplant patients, in particular, are at increased risk of colonization and infection with MDRO because of immunomodulatory therapies, healthcare exposure, increased antibiotic exposure and surgical manipulation of mucosa. Furthermore, chronic kidney disease and dialysis therapy leading up to transplant has been shown to be associated with alterations in both the intestinal and periodontal microbiome. Understanding the evolution of the disruption in the intestinal microbiome in both kidney transplant recipients and healthy kidney transplant donors during the time of transplant surgical prophylaxis will give valuable insight into further avenues for research and possible interventions that may mitigate the risk of MDRO colonization.
This is a prospective, observational, and non-interventional pilot study which aims to enroll 100 adult renal transplant recipients and 100 adult renal transplant donors. Participants will provide stool samples and anal swab samples, and will complete dietary questionnaires. Participants may also choose to take part in an optional sub-study which involves banking leftover stool for future research use.
The diversity change of the intestinal microbiota over time will be assessed at the screening visit, Post-Operative Day 2; Post-Discharge Day 15 and Post-Discharge Day 30. Participants will be followed by way of medical record review for 24 weeks post-surgery.
This study is designed to understand the intestinal microbiota diversity in the setting of renal transplant surgery and the clinical significance of antibiotic use and the associated resistome (collection of all antibiotic resistance genes and precursors within a sample). Information learned from this study will be used to guide the design of future clinical trials.
- Conditions
- Renal Transplant
- Being tested
- Stool Specimen Collection, Anal Swab Sampling, Short Diet Assessment (SDA), NHANES Dietary Screener Questionnaire (DSQ)
- Keywords
- Microbiota composition, Kidney transplant recipient, Kidney transplant donor, Antibiotics, Drug resistance, Transplantation surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stool Specimen CollectionOther
Participants will provide a stool sample at baseline (pre-operation) and 30 days after the transplant operation. Stool specimens will be self-collected by the participant.
Anal Swab SamplingOther
Anal swabs will be collected prior to surgery (baseline) and at post-operation days 2, 15, and 30. Participants whose planned hospitalization duration is extended from the pre-surgical plan will have an additional, optional, anal swab collected 2 days prior to their anticipated hospital discharge date. Anal swabs will be collected by the study team, except for the standard of care post-operative appointment (30 days after the operation) for the living donors who will collect their own samples.
Short Diet Assessment (SDA)Other
The study coordinator will administer the Short Diet Assessment (SDA) to participants prior to surgery at baseline and post-operation days 2, 15, and 30. Participants whose planned hospital length of stay is extended from the pre-surgical plan will complete the questionnaire 2 days prior to their anticipated hospital discharge date.
NHANES Dietary Screener Questionnaire (DSQ)Other
The National Health and Nutrition Examination Survey (NHANES) 2009-2010 Dietary Screener Questionnaire will be completed on Post-Operative Day 2. The questionnaire asks about foods consumed during the past 30 days. There are 25 items on the questionnaire and additional questions may be asked depending on responses provided. The questionnaire will be self-administered or administered by a study team member.
| Study group | Role | What they receive |
|---|---|---|
| Renal transplant recipient | Participants who are scheduled for a planned renal transplant as the recipient of the kidney.
All participants will complete the following interventions:
* Stool Specimen Collection
* Anal Swab Sampling
* Short Diet Assessment (SDA)
* NHANES Dietary Screener Questionnaire (DSQ) Receives: Other: Stool Specimen Collection; Other: Anal Swab Sampling; Other: Short Diet Assessment (SDA); Other: NHANES Dietary Screener Questionnaire (DSQ) | |
| Renal transplant donor | Participants who are scheduled for a planned renal transplant as the donor of the kidney.
All participants will complete the following interventions:
* Stool Specimen Collection
* Anal Swab Sampling
* Short Diet Assessment (SDA)
* NHANES Dietary Screener Questionnaire (DSQ) Receives: Other: Stool Specimen Collection; Other: Anal Swab Sampling; Other: Short Diet Assessment (SDA); Other: NHANES Dietary Screener Questionnaire (DSQ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in microbiota composition
To understand the overall impact of surgical prophylaxis on intestinal microbiota composition in the setting of renal transplant surgery, the distribution and relative abundance of bacterial and fungal taxa for each collected sample will be described. A genus of strain will be considered predominant if it represents at least 30% of all genus or strains of microbiota within the stool sample.
Measured: Baseline to Postoperative Day 30
Change in microbiota diversity
To understand the overall impact of surgical prophylaxis on intestinal microbiota diversity in the setting of renal transplant surgery, measures of α- and β-diversity of the intestinal microbiota will be utilized. The maximum percentage of all genes identified included within the same taxon will be determined from each stool sample.
Measured: Baseline to Postoperative Day 30
Change in microbiota taxonomy
To understand the overall impact of surgical prophylaxis on intestinal microbiota taxonomy, in the setting of renal transplant surgery, the collected specimens will be used for taxonomic composition determination of bacteria and fungi. Whole genome shotgun metagenomic sequencing will be performed on an Illumina Miseq (or HiSeq). A short read mapper will be used to screen out and discard human sequences from each stool sample and subsequently Metaphlan and KRAKEN are used for taxonomic composition determination.
Measured: Baseline to Postoperative Day 30
Change in microbiota resistome
To understand the overall impact of surgical prophylaxis on intestinal microbiota resistance, in the setting of renal transplant surgery, the study samples collected will be used to provide a summary of the overall number and diversity of bacterial and fungal resistance genes, including any new acquisition.
Measured: Baseline to Postoperative Day 30
Secondary outcomes (3)
Microbiota composition in renal dialysis patients
To understand the intestinal microbiota composition in patients receiving renal dialysis, the distribution and relative abundance of bacterial and fungal taxa for each collected sample will be described. A genus of strain will be considered predominant if it represents at least 30% of all genus or strains of microbiota within the stool sample collected at baseline (prior to renal transplant).
Measured: Baseline
Microbiota diversity in renal dialysis patients
To understand the intestinal microbiota Alpha and Beta diversity in patients receiving renal dialysis, the maximum percentage of all genes identified included within the same taxon will be determined from the study samples collected at baseline (prior to renal transplant).
Measured: Baseline
Microbiota resistome in renal dialysis patients
To understand the intestinal microbiota resistance in patients receiving renal dialysis, the study samples collected at baseline (prior to renal transplant) will be used to provide a summary of the overall number and diversity of bacterial resistance genes.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2017 (estimated)
- Study start2 Oct 2017
- Primary completion10 Jan 2019
- Study completion10 Jan 2019
Why it stopped: Study halted prematurely due to lack of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal TransplantStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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
- Other
- Time perspective
- Prospective
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Responsible party
- Principal investigator, Colleen S. Kraft, Emory University
- Investigators
- Colleen S Kraft, MD, MSc, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03043339
- Sponsor's protocol ID
- IRB00092450
- Other IDs
- 16IPA1609418, 16IPA1609428, CDC-IRB00092450
- Acronym
- COMET-DR
- Status last verified
- Jun 2024
- First submitted
- 2 Feb 2017
- Last updated
- 26 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization Of the Intestinal Microbiome Evolution After Kidney Transplant Donation or Receipt
- ClinicalTrials.gov ID
- NCT03043339
- Acronym / sponsor ID
- COMET-DR / IRB00092450
- Conditions
- Renal Transplant
- Keywords
- Microbiota composition, Kidney transplant recipient, Kidney transplant donor, Antibiotics, Drug resistance, Transplantation surgery
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Study halted prematurely due to lack of funding.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention
- Study start
- 2 Oct 2017 (actual)
- Primary completion
- 10 Jan 2019 (actual)
- Study completion
- 10 Jan 2019 (actual)
- First posted
- 6 Feb 2017 (estimated)
- 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.
This is a hypothesis-generating pilot study. The intent is to model the impact of perioperative practices on the intestinal microbiome and possibly associate these conditions with the final microbiome status (e.g., number of resistance genes and diversity associated with perioperative practices and preoperative microbiome status). Participants will include individuals who are having surgery to either receive or donate a kidney. To determine the diversity change of the intestinal microbiota over time, rectal swabs will be collected before surgery and at several time points after surgery, with the last swab collected 30 days after surgery.
This pilot study is to obtain preliminary data to support the rationale and design for a subsequent clinical trial. This study is designed to understand the intestinal microbiota diversity in the setting of renal transplant surgery and the clinical significance of antibiotic use and the associated resistome (collection of all antibiotic resistance genes and precursors within a sample).
Detailed description
The emergence of multidrug resistant organisms (MDROs) is a growing threat to global public health and is associated with high morbidity and mortality in both the general and solid organ transplant population. Intestinal microbiota diversity can provide functional and spatial barriers to bacterial and fungal MDRO colonization, and loss of diversity is associated with increased MDRO colonization. Dysbiosis is a state of loss of microbiota diversity and a single antibiotic treatment course can cause significant disruption in microbiota diversity, even in otherwise healthy individuals. This disruption can promote the growth of pathogenic and multidrug-resistant bacteria and fungi. Transplant patients, in particular, are at increased risk of colonization and infection with MDRO because of immunomodulatory therapies, healthcare exposure, increased antibiotic exposure and surgical manipulation of mucosa. Furthermore, chronic kidney disease and dialysis therapy leading up to transplant has been shown to be associated with alterations in both the intestinal and periodontal microbiome. Understanding the evolution of the disruption in the intestinal microbiome in both kidney transplant recipients and healthy kidney transplant donors during the time of transplant surgical prophylaxis will give valuable insight into further avenues for research and possible interventions that may mitigate the risk of MDRO colonization.
This is a prospective, observational, and non-interventional pilot study which aims to enroll 100 adult renal transplant recipients and 100 adult renal transplant donors. Participants will provide stool samples and anal swab samples, and will complete dietary questionnaires. Participants may also choose to take part in an optional sub-study which involves banking leftover stool for future research use.
The diversity change of the intestinal microbiota over time will be assessed at the screening visit, Post-Operative Day 2; Post-Discharge Day 15 and Post-Discharge Day 30. Participants will be followed by way of medical record review for 24 weeks post-surgery.
This study is designed to understand the intestinal microbiota diversity in the setting of renal transplant surgery and the clinical significance of antibiotic use and the associated resistome (collection of all antibiotic resistance genes and precursors within a sample). Information learned from this study will be used to guide the design of future clinical trials.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Renal transplant recipient | – | Other: Stool Specimen Collection, Other: Anal Swab Sampling, Other: Short Diet Assessment (SDA), Other: NHANES Dietary Screener Questionnaire (DSQ)Participants who are scheduled for a planned renal transplant as the recipient of the kidney. All participants will complete the following interventions: * Stool Specimen Collection * Anal Swab Sampling * Short Diet Assessment (SDA) * NHANES Dietary Screener Questionnaire (DSQ) |
| Renal transplant donor | – | Other: Stool Specimen Collection, Other: Anal Swab Sampling, Other: Short Diet Assessment (SDA), Other: NHANES Dietary Screener Questionnaire (DSQ)Participants who are scheduled for a planned renal transplant as the donor of the kidney. All participants will complete the following interventions: * Stool Specimen Collection * Anal Swab Sampling * Short Diet Assessment (SDA) * NHANES Dietary Screener Questionnaire (DSQ) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Renal transplant recipients and living donors
Key inclusion criteria (9 listed)
- Ability to understand and the willingness to sign a written informed consent document.
- Ability and willingness to comply with study protocol requirements.
- Completed Verbal Screening Form
- Planned kidney donation or planned receipt of a living donor kidney transplant within 28 days from time of written informed consent.
- If performance status is known, a score of any of the following:
Key exclusion criteria (7 listed)
- Any condition that, in the opinion of the investigator, might interfere with study objectives or limit compliance with study requirements, including but not limited to:
- Planned or actual receipt of a deceased donor kidney transplant.
- Prior kidney transplant that still requires active immunosuppressive treatment or intervention.
- Presence of diverting ileostomy or colostomy.
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 |
|---|---|---|
| Stool Specimen CollectionParticipants will provide a stool sample at baseline (pre-operation) and 30 days after the transplant operation. Stool specimens will be self-collected by the participant. | Other | Renal transplant donor, Renal transplant recipient |
| Anal Swab SamplingAnal swabs will be collected prior to surgery (baseline) and at post-operation days 2, 15, and 30. Participants whose planned hospitalization duration is extended from the pre-surgical plan will have an additional, optional, anal swab collected 2 days prior to their anticipated hospital discharge date. Anal swabs will be collected by the study team, except for the standard of care post-operative appointment (30 days after the operation) for the living donors who will collect their own samples. | Other | Renal transplant donor, Renal transplant recipient |
| Short Diet Assessment (SDA)The study coordinator will administer the Short Diet Assessment (SDA) to participants prior to surgery at baseline and post-operation days 2, 15, and 30. Participants whose planned hospital length of stay is extended from the pre-surgical plan will complete the questionnaire 2 days prior to their anticipated hospital discharge date. | Other | Renal transplant donor, Renal transplant recipient |
| NHANES Dietary Screener Questionnaire (DSQ)The National Health and Nutrition Examination Survey (NHANES) 2009-2010 Dietary Screener Questionnaire will be completed on Post-Operative Day 2. The questionnaire asks about foods consumed during the past 30 days. There are 25 items on the questionnaire and additional questions may be asked depending on responses provided. The questionnaire will be self-administered or administered by a study team member. | Other | Renal transplant donor, Renal transplant recipient |
Primary outcome
Change in microbiota composition
Time frame: Baseline to Postoperative Day 30
To understand the overall impact of surgical prophylaxis on intestinal microbiota composition in the setting of renal transplant surgery, the distribution and relative abundance of bacterial and fungal taxa for each collected sample will be described. A genus of strain will be considered predominant if it represents at least 30% of all genus or strains of microbiota within the stool sample.
Change in microbiota diversity
Time frame: Baseline to Postoperative Day 30
To understand the overall impact of surgical prophylaxis on intestinal microbiota diversity in the setting of renal transplant surgery, measures of α- and β-diversity of the intestinal microbiota will be utilized. The maximum percentage of all genes identified included within the same taxon will be determined from each stool sample.
Change in microbiota taxonomy
Time frame: Baseline to Postoperative Day 30
To understand the overall impact of surgical prophylaxis on intestinal microbiota taxonomy, in the setting of renal transplant surgery, the collected specimens will be used for taxonomic composition determination of bacteria and fungi. Whole genome shotgun metagenomic sequencing will be performed on an Illumina Miseq (or HiSeq). A short read mapper will be used to screen out and discard human sequences from each stool sample and subsequently Metaphlan and KRAKEN are used for taxonomic composition determination.
Change in microbiota resistome
Time frame: Baseline to Postoperative Day 30
To understand the overall impact of surgical prophylaxis on intestinal microbiota resistance, in the setting of renal transplant surgery, the study samples collected will be used to provide a summary of the overall number and diversity of bacterial and fungal resistance genes, including any new acquisition.
3 secondary outcomes
Microbiota composition in renal dialysis patients
Time frame: Baseline
Microbiota diversity in renal dialysis patients
Time frame: Baseline
Microbiota resistome in renal dialysis patients
Time frame: Baseline
Results and safety
The study was stopped early (reason given: Study halted prematurely due to lack of funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2024.
- Individual participant dataSharing planned: No
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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.
Colleen S Kraft, MD, MSc principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Renal Transplant, run by Emory University at 2 sites in United States.
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 9 inclusion and 7 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: stopped early, as of the sponsor's last update on 26 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
The study was stopped early (reason given: Study halted prematurely due to lack of funding.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in microbiota composition (time frame: Baseline to Postoperative Day 30). The study lists 4 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 26 Jun 2024.