The Gut Microbiome and Serum Metabolites As a Biological Mechanism Underlying Pain in Kidney Transplantation

NCT06206486 | Recruiting

• 1 other identifier: 2023-0193
• Study Type: observational
• Target: 133
• Locations: 1 country
• Sites: 1

Brief Summary

Study Summary Nearly half (47%) of people with end-stage kidney disease (ESKD) whose kidney function is restored after kidney transplantation experience chronic pain compared to 19% of adults in the US general population. Pain is associated with comorbid fatigue, depression and anxiety, and withdrawal from usual physical and social activities; resulting in an inability to participate in and enjoy life. Severe pain can result in nonadherence to immunosuppression and treatment protocols and result in an increased risk of rejection, graft loss, and mortality. The role of symbiotic microbes (microbiota) in the gastrointestinal tract, and their functional genes (microbiome), is well established in diseases involving pain. Diet and stress play a major role in synthesis of signaling molecules critical to immunologic, metabolic, and endocrine pathways regulating chronic pain. Dietary patterns change dramatically after transplantation, as recipients move from a restricted "renal" diet to a regular diet, often resulting in increased consumption of foods high in sugars and fat. Moreover, psychological stress significantly impairs the function of the microbiome, initiating biological pathways involved in pain, leading to a disproportionate pain burden. Because the microbiome, serum metabolites, and pain are dynamic, our novel investigation will employ a prospective repeated measures design to interrogate the dynamic temporal relationships between the microbiome, metabolites associated with pathways regulating pain, transplantation factors (e.g. immunosuppression, kidney function), changing dietary patterns, and perceived stress, on pain scores before and after kidney transplantation. The investigators posit the gut microbiome, and its byproducts, may partially explain the underlying biological mechanisms of pain Interference in kidney disease. The investigators will address three aims: 1) To determine differential dynamic temporal relationships between microbial composition/functional genes and circulating serum metabolites in KTRs with pain vs no pain, 2) To determine the moderation effects of diet and perceived stress on dynamic temporal relationships between microbiome features, serum metabolites, and pain scores among KTRs, and 3) To use machine learning algorithms to identify host-microbial interactions that are causally linked to pain interference among KTRs. Because kidney function is restored, the kidney transplant model is powerful to study the longitudinal relationships between the microbiome, circulating metabolites and chronic pain in people with ESKD to develop patient-centered interventions to treat pain across the spectrum of CKD.

Conditions

Kidney Transplant Symptoms; Gut Microbiome

Outcome Measures

Primary Outcomes (1)

• PROMIS

  Patient Reported Outcomes Measurement System

  baseline, 3 months, 6 months (T scores range form 0-100, higher scores indicate worse level of symptoms).

Secondary Outcomes (1)

• PSS

  baseline, 3 months, 6 months

Other Outcomes (1)

• Vioscreen

  baseline, 3 months, 6 months

Interventions

no intervention, observational OTHER

This study is observational. No intervention description available.

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

Kidney Transplant Recipients

You may qualify if:

• Receiving a kidney transplant at the University of Illinois Hospital \& Health Sciences System (UI Health) Transplant Center at the University of Illinois Chicago (UIC),
• years of age or older (adult), and
• Understand the study process and provide written informed consent to participate.

You may not qualify if:

• Having taken systemic antimicrobials (except prophylactic penicillin) in the preceding 4 weeks.
• Having received a previous solid organ transplant.
• History of colon cancer or of an inflammatory bowel disease.
• Planning to receive a multiorgan transplant (e.g., simultaneous pancreas and kidney transplant).
• Having a history of Clostridium difficile infection in the preceding 8 weeks.

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

UI Health

Chicago, Illinois, 60612, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

bacterial DNA for fecal samples to assess microbiome features. No human DNA will be retained for this study

Central Study Contacts

Mark Lockwood

CONTACT

314-604-2050; lockmar@uic.edu

Gullermo Zamora

CONTACT

7732208631; gzamor2@uic.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 16, 2024
• Study Start: October 9, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)