Gut Microbiome and p-Inulin in Hemodialysis

A Multi-center Study to Characterize the Gut Microbiome of Individuals With End-stage Renal Disease Treated With Maintenance Hemodialysis, and to Explore Effects of P-inulin on the Gut Microbiome

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.

Study Overview

• Status: Completed
• Conditions: End-Stage Renal Disease; Gut Microbiome Dysbiosis
• Intervention / Treatment: Dietary supplement: p-inulin

Detailed Description

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
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The George Washington University
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Kidney Research Institute, University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single arm; This is a sequential study in which participants are observed (no intervention) for 8 weeks (pre-treatment), then participants self-administer p-inulin 8g orally twice daily for 12 weeks (treatment phase), and then observed for a final 8 weeks during which no treatment was administered (post-treatment).	Dietary supplement: p-inulin; 12 week self-administered treatment phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	28 weeks
Within Participant Variability in Plasma 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.	28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	-Early discontinuation of p-inulin	12 weeks
Number of Participants Who Reduce the Dose of P-inulin (Tolerability Outcome)	-Reduction in p-inulin dose	12 weeks
Number of Participants With Adverse Events (Safety Outcome)	-Adverse events per participant related to treatment as coded using the Medical Dictionary for Regulatory Activities (MedDRA) Coding System	28 weeks
Number of Serious Adverse Events (Safety Outcome)	Serious adverse events categorized by body systems, related to treatment as coded using the Medical Dictionary for Regulatory Activities (MedDRA) Coding System	28 weeks
Rate of Enrollment Refusal (Feasibility Outcome)	Enrollment refusal rate	1 year
Stool Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)	Percent of expected completed protocol-specified stool sample collections	28 weeks
Blood Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)	Proportion of completed blood sample collections	28 weeks
Adherence Rate of P-inulin Use (Feasibility Outcome)	Proportion of p-inulin packets used	12 weeks
Rate of Study Withdrawal (Feasibility Outcome)	Number of withdrawals during each phase of the study	28 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Brigham and Women's Hospital; University of Washington; Vanderbilt University; George Washington University
• Investigators: Principal Investigator: Laura Dember, MD, University of Pennsylvania; Principal Investigator: J Richard Landis, PhD, Perelman School of Medicine at the University of Pennsylvania

Publications and helpful links

General Publications

• Raj DS, Sohn MB, Charytan DM, Himmelfarb J, Ikizler TA, Mehrotra R, Ramezani A, Regunathan-Shenk R, Hsu JY, Landis JR, Li H, Kimmel PL, Kliger AS, Dember LM; Hemodialysis Novel Therapies Consortium. The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study. Kidney360. 2021 Jan 15;2(3):445-455. doi: 10.34067/KID.0006132020. eCollection 2021 Mar 25.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): January 24, 2017
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: August 19, 2015
• First Submitted That Met QC Criteria: October 7, 2015
• First Posted (Estimate): October 9, 2015

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: September 22, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: gut microbiome; hemodialysis; p-inulin
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Dysbiosis
• Other Study ID Numbers: 823162; U01DK099919 (U.S. NIH Grant/Contract)