Gut Microbiome and p-Inulin in Hemodialysis

End-Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02572882
• Other study ID #: 823162
• Secondary ID: U01DK099919
• Status: Completed
• Phase: N/A
• Start date: October 2015
• Est. completion date: January 2019

Study information

• Verified date: September 2022
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: January 2019
• Est. primary completion date: January 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Dysbiosis
• End-Stage Renal Disease
• Gut Microbiome Dysbiosis
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Dietary Supplement:
• p-inulin
12 week self-administered treatment phase

Locations

Country	Name	City	State
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	The George Washington University	Washington	District of Columbia

Sponsors (6)

Lead Sponsor	Collaborator
University of Pennsylvania	Brigham and Women's Hospital, George Washington University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Washington, Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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.
Secondary	Number of Participants Who Discontinued Use of P-inulin (Tolerability Outcome)	-Early discontinuation of p-inulin	12 weeks
Secondary	Number of Participants Who Reduce the Dose of P-inulin (Tolerability Outcome)	-Reduction in p-inulin dose	12 weeks
Secondary	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
Secondary	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
Secondary	Rate of Enrollment Refusal (Feasibility Outcome)	Enrollment refusal rate	1 year
Secondary	Stool Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)	Percent of expected completed protocol-specified stool sample collections	28 weeks
Secondary	Blood Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)	Proportion of completed blood sample collections	28 weeks
Secondary	Adherence Rate of P-inulin Use (Feasibility Outcome)	Proportion of p-inulin packets used	12 weeks
Secondary	Rate of Study Withdrawal (Feasibility Outcome)	Number of withdrawals during each phase of the study	28 weeks