Clinical trial NCT03043339: Characterization Of the Intestinal Microbiome Evolution After Kidney Transplant Donation or Receipt
Official title: Characterization Of the Intestinal Microbiome Evolution After Kidney Transplant Donation or Receipt
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Renal Transplant
Keywords: Microbiota composition
Kidney transplant recipient
Kidney transplant donor
Antibiotics
Drug resistance
Transplantation surgery
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2017-02-06
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Renal transplant recipients and living donors

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* 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)
  * 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in microbiota composition
timeFrame: Baseline to Postoperative Day 30
measure: Change in microbiota diversity
timeFrame: Baseline to Postoperative Day 30
measure: Change in microbiota taxonomy
timeFrame: Baseline to Postoperative Day 30
measure: Change in microbiota resistome
timeFrame: Baseline to Postoperative Day 30
Secondary outcomes:
measure: Microbiota composition in renal dialysis patients
timeFrame: Baseline
measure: Microbiota diversity in renal dialysis patients
timeFrame: Baseline
measure: Microbiota resistome in renal dialysis patients
timeFrame: Baseline
Other outcomes:
measure: Compare microbiota composition of donors and recipients
timeFrame: Baseline
measure: Compare microbiota diversity of donors and recipients
timeFrame: Baseline
measure: Compare microbiota taxonomy of donors and recipients
timeFrame: Baseline
measure: Compare microbiota resistome of donors and recipients
timeFrame: Baseline
Locations:
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Colleen S Kraft, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: