Gut Microbiome and p-Inulin in Hemodialysis

University of Pennsylvania13 enrolled

Overview

The Microbiome trial is a non-randomized, open-label, sequential, multi-center study of p-inulin for patients with hemodialysis-dependent end-stage renal disease.

This primary objective of this exploratory study is to characterize the safety and tolerability of p-inulin (Prebiotin®, provided by JGI Medical) in altering the composition and function of the human gut microbiome, thereby reducing the generation of gut-derived uremic toxins, improving gut barrier function and attenuating systemic inflammation in patients treated with maintenance hemodialysis. The study also aims to assess the feasibility of conducting a full-scale trial of p-inulin. The primary efficacy parameters of the trial will be intra- and inter-participant variability in gut metabolites and bacterial composition. Secondary parameters of interest include tolerability and safety of p-inulin, willingness of hemodialysis patients to enroll in a study requiring repeated collection of stool samples, and participant adherence to agent treatment and specimen collection schedules.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

End-Stage Renal Disease Gut Microbiome Dysbiosis

Interventions

p-inulinDIETARY_SUPPLEMENT

12 week self-administered treatment phase

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Maintenance hemodialysis therapy for end-stage renal disease * At least 18 years of age * At least 90 days since hemodialysis initiation * Self-reported average stool frequency of at least 1 every other day * For women of childbearing potential, willingness to use a highly effective method of birth control for up to 4 weeks after the last dose of p-inulin. * Ability to provide consent Exclusion Criteria: * Use of prebiotics or probiotics during the past 8 weeks * Consumption of probiotic yogurt during the past 2 weeks * Use of antibiotics within the past 8 weeks * Presence of HIV infection, chronic wound infection, osteomyelitis, or current hemodialysis * Inflammatory bowel disease, chronic diarrhea, current C. difficile infection * Cirrhosis or chronic active hepatitis * Anticipated kidney transplantation, change to peritoneal dialysis, or transfer to another dialysis unit within 9 months * Expected survival less than 9 months * Pregnancy, anticipated pregnancy, or breastfeeding * Incarceration * Participation in another intervention study * Severe anemia defined as hemoglobin \<9.0 g/dl within the past 4 weeks as documented in the dialysis unit patient record

Locations (4)

The George Washington University

Washington D.C., District of Columbia, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Kidney Research Institute, University of Washington

Seattle, Washington, United States

Outcomes

Primary Outcomes

Within Participant Variability in Microbiome Composition by Treatment Phase

The weighted UniFrac distance was used to compute the distances for each sample. Weighted UniFrac distance uses species abundance information and weights the branch length with abundance difference. Weighted UniFrac distance is most sensitive to detect change in abundant lineages since it uses absolute abundance difference in its definition.

Time frame: 28 weeks

Within Participant Variability in Stool Metabolome by Treatment Phase

The Euclidean distance was used to compute the distances for each sample. The Euclidean distance is defined as the distance between two points. Differences between samples were determined on the basis of distances from the initial measurements to account for participant-level differences in initial abundance of microorganisms.

Time frame: 28 weeks

Within Participant Variability in Plasma Metabolome by Treatment Phase

Time frame: 28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment)

Secondary Outcomes

Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) (Safety Outcome)

Gastrointestinal symptoms as measure by the Gastrointestinal Symptom Rating Scale (GSRS). The GSRS total score is the sum of 15 0-3 items where 0 indicates absence and 3 an extreme degree of the symptom. A higher score indicates worse outcome. The minimum score is 0, the maximum score is 45.

Time frame: GSRS was assessed at Weeks 0, 4, 8, 12, 16, 20, 24 and 28.

Number of Participants Who Discontinued Use of P-inulin (Tolerability Outcome)

Data from ClinicalTrials.gov

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