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

NCT ID: NCT03043339

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 3 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-10-02
• Study Completion Date: 2019-01-10

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.

Conditions

Renal Transplant

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

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)

Stool Specimen Collection

Intervention Type: 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.

Anal Swab Sampling

Intervention Type: 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.

Short Diet Assessment (SDA)

Intervention Type: 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)

Intervention Type: 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

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)

Stool Specimen Collection

Intervention Type: 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.

Anal Swab Sampling

Intervention Type: 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.

Short Diet Assessment (SDA)

Intervention Type: 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)

Intervention Type: 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.

Interventions

Stool Specimen Collection

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.

Intervention Type: OTHER

Anal Swab Sampling

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.

Intervention Type: OTHER

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.

Intervention Type: OTHER

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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Colleen S. Kraft

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Colleen S Kraft, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

The Emory Clinic

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

16IPA1609418

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

16IPA1609428

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CDC-IRB00092450

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00092450

Identifier Type: -

Identifier Source: org_study_id