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Gut Microbiome and p-Inulin in Hemodialysis

Primary Purpose

End-Stage Renal Disease, Gut Microbiome Dysbiosis

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
p-inulin
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for End-Stage Renal Disease focused on measuring hemodialysis, p-inulin, gut microbiome

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The George Washington University
  • Brigham and Women's Hospital
  • Vanderbilt University Medical Center
  • Kidney Research Institute, University of Washington

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Single arm

Arm Description

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).

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
Number of Participants Who Discontinued Use of P-inulin (Tolerability Outcome)
-Early discontinuation of p-inulin
Number of Participants Who Reduce the Dose of P-inulin (Tolerability Outcome)
-Reduction in p-inulin dose
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
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
Rate of Enrollment Refusal (Feasibility Outcome)
Enrollment refusal rate
Stool Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)
Percent of expected completed protocol-specified stool sample collections
Blood Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)
Proportion of completed blood sample collections
Adherence Rate of P-inulin Use (Feasibility Outcome)
Proportion of p-inulin packets used
Rate of Study Withdrawal (Feasibility Outcome)
Number of withdrawals during each phase of the study

Full Information

First Posted
August 19, 2015
Last Updated
September 22, 2022
Sponsor
University of Pennsylvania
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Brigham and Women's Hospital, George Washington University, Vanderbilt University, University of Washington
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1. Study Identification

Unique Protocol Identification Number
NCT02572882
Brief Title
Gut Microbiome and p-Inulin in Hemodialysis
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
October 2015 (Actual)
Primary Completion Date
January 24, 2017 (Actual)
Study Completion Date
January 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Brigham and Women's Hospital, George Washington University, Vanderbilt University, University of Washington

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-Stage Renal Disease, Gut Microbiome Dysbiosis
Keywords
hemodialysis, p-inulin, gut microbiome

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
This is a sequential trial that included three sequential phases: 1. Pre-treatment phase: 8 weeks during which no treatment was administered 2. p-Inulin phase: 12 weeks during which p-inulin was administered 8g orally twice daily 3. Post-treatment phase: 8 weeks during which no treatment was administered. Eleven of the 13 participants in the p-inulin phase entered the post-treatment phase. The other two withdrew prior to the post-treatment phase.
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single arm
Arm Type
Other
Arm Description
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).
Intervention Type
Dietary Supplement
Intervention Name(s)
p-inulin
Intervention Description
12 week self-administered treatment phase
Primary Outcome Measure Information:
Title
Within Participant Variability in Microbiome Composition by Treatment Phase
Description
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
Title
Within Participant Variability in Stool Metabolome by Treatment Phase
Description
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
Title
Within Participant Variability in Plasma Metabolome by Treatment Phase
Description
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 (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment)
Secondary Outcome Measure Information:
Title
Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) (Safety Outcome)
Description
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.
Title
Number of Participants Who Discontinued Use of P-inulin (Tolerability Outcome)
Description
-Early discontinuation of p-inulin
Time Frame
12 weeks
Title
Number of Participants Who Reduce the Dose of P-inulin (Tolerability Outcome)
Description
-Reduction in p-inulin dose
Time Frame
12 weeks
Title
Number of Participants With Adverse Events (Safety Outcome)
Description
-Adverse events per participant related to treatment as coded using the Medical Dictionary for Regulatory Activities (MedDRA) Coding System
Time Frame
28 weeks
Title
Number of Serious Adverse Events (Safety Outcome)
Description
Serious adverse events categorized by body systems, related to treatment as coded using the Medical Dictionary for Regulatory Activities (MedDRA) Coding System
Time Frame
28 weeks
Title
Rate of Enrollment Refusal (Feasibility Outcome)
Description
Enrollment refusal rate
Time Frame
1 year
Title
Stool Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)
Description
Percent of expected completed protocol-specified stool sample collections
Time Frame
28 weeks
Title
Blood Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)
Description
Proportion of completed blood sample collections
Time Frame
28 weeks
Title
Adherence Rate of P-inulin Use (Feasibility Outcome)
Description
Proportion of p-inulin packets used
Time Frame
12 weeks
Title
Rate of Study Withdrawal (Feasibility Outcome)
Description
Number of withdrawals during each phase of the study
Time Frame
28 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laura Dember, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
J Richard Landis, PhD
Organizational Affiliation
Perelman School of Medicine at the University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
The George Washington University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02120
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Kidney Research Institute, University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35369018
Citation
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.
Results Reference
derived

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Gut Microbiome and p-Inulin in Hemodialysis

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