Gut Microbiome and p-Inulin in Hemodialysis

Not Applicable

Completed

• Conditions: Gut Microbiome Dysbiosis; End-Stage Renal Disease
• Interventions: Dietary Supplement: p-inulin

• Registration Number: NCT02572882
• Lead Sponsor: University of Pennsylvania

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-08-19
• Study Start: 2015-10
• Study First Submitted QC: 2015-10-07
• Study First Posted: 2015-10-09
• Primary Completion: 2017-01-24
• Study Completion: 2019-01
• Results First Submitted: 2021-07-22
• Status Verified: 2022-09
• Results First Submitted QC: 2022-09-22
• Last Update Submitted: 2022-09-22
• Results First Posted: 2022-10-20
• Last Update Posted: 2022-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single arm	p-inulin	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).

Primary Outcome Measures

Name	Time	Method
Within Participant Variability in Microbiome Composition by Treatment Phase	28 weeks	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.
Within Participant Variability in Plasma Metabolome by Treatment Phase	28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment)	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.
Within Participant Variability in Stool Metabolome by Treatment Phase	28 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Discontinued Use of P-inulin (Tolerability Outcome)	12 weeks	-Early discontinuation of p-inulin
Rate of Enrollment Refusal (Feasibility Outcome)	1 year	Enrollment refusal rate
Adherence Rate of P-inulin Use (Feasibility Outcome)	12 weeks	Proportion of p-inulin packets used
Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) (Safety Outcome)	GSRS was assessed at Weeks 0, 4, 8, 12, 16, 20, 24 and 28.	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.
Number of Participants Who Reduce the Dose of P-inulin (Tolerability Outcome)	12 weeks	-Reduction in p-inulin dose
Number of Participants With Adverse Events (Safety Outcome)	28 weeks	-Adverse events per participant related to treatment as coded using the Medical Dictionary for Regulatory Activities (MedDRA) Coding System
Number of Serious Adverse Events (Safety Outcome)	28 weeks	Serious adverse events categorized by body systems, related to treatment as coded using the Medical Dictionary for Regulatory Activities (MedDRA) Coding System
Stool Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)	28 weeks	Percent of expected completed protocol-specified stool sample collections
Blood Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)	28 weeks	Proportion of completed blood sample collections
Rate of Study Withdrawal (Feasibility Outcome)	28 weeks	Number of withdrawals during each phase of the study

Trial Locations

Locations (4)

Kidney Research Institute, University of Washington; 🇺🇸 Seattle, Washington, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

The George Washington University; 🇺🇸 Washington, District of Columbia, United States