Characterization Of the Intestinal Microbiome Evolution After Kidney Transplant Donation or Receipt

NCT03043339 | Terminated DMC

• 4 other identifiers: IRB0009245016IPA160941816IPA1609428CDC-IRB00092450
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 2

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).

Conditions

Renal Transplant

Keywords

Microbiota composition; Kidney transplant recipient; Kidney transplant donor; Antibiotics; Drug resistance; Transplantation surgery

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Baseline to Postoperative Day 30

Secondary Outcomes (3)

• Microbiota composition in renal dialysis patients

  Baseline

• Microbiota diversity in renal dialysis patients

  Baseline

• Microbiota resistome in renal dialysis patients

  Baseline

Other Outcomes (4)

• Compare microbiota composition of donors and recipients

  Baseline

• Compare microbiota diversity of donors and recipients

  Baseline

• Compare microbiota taxonomy of donors and recipients

  Baseline

Study Arms (2)

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)

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)

Other: Stool Specimen Collection; Other: Anal Swab Sampling; Other: Short Diet Assessment (SDA); Other: NHANES Dietary Screener Questionnaire (DSQ)

Interventions

Stool Specimen Collection OTHER

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.

Renal transplant donor; Renal transplant recipient

Anal Swab Sampling OTHER

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.

Renal transplant donor; Renal transplant recipient

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.

Renal transplant donor; Renal transplant recipient

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.

Renal transplant donor; Renal transplant recipient

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Renal transplant recipients and living donors

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (2)

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Emory University Hospital

Atlanta, Georgia, 30324, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Specimens collected through anal swabs and stool samples will be stored until DNA extraction can occur. DNA analysis of the microbiome will occur; DNA of the participants will not be examined.

Study Officials

• Colleen S Kraft, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: February 6, 2017
• Study Start: October 2, 2017
• Primary Completion: January 10, 2019
• Study Completion: January 10, 2019
• Last Updated: June 26, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)