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Gut Microbiome and p-Inulin in Hemodialysis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02572882
Recruitment Status : Completed
First Posted : October 9, 2015
Last Update Posted : February 6, 2019
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Brigham and Women's Hospital
George Washington University
Vanderbilt University
University of Washington
Information provided by (Responsible Party):
University of Pennsylvania

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

Condition or disease Intervention/treatment Phase
End-Stage Renal Disease Gut Microbiome Dysbiosis Dietary Supplement: p-inulin Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : October 2015
Actual Primary Completion Date : January 24, 2017
Actual Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Inulin

Arm Intervention/treatment
No Intervention: Pre-treatment
This arm is the 8-week observation period before the p-inulin treatment phase.
Experimental: p-inulin
This arm is the 12 week p-inulin treatment phase (8 grams twice daily, oral).
Dietary Supplement: p-inulin
12 week self-administered treatment phase

No Intervention: Post-treatment
This arm is the 8-week observation period after the p-inulin treatment phase.



Primary Outcome Measures :
  1. Within Participant, Within Phase Variability in Relative Abundance of Metabolites (Efficacy Outcome) [ Time Frame: 28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment) ]

    Microbiome characterization endpoints are within-participant variability in the metabolomic profile and targeted metabolites / inflammatory markers.

    Stool samples will be collected at baseline, once weekly during weeks 1-7, 10-19, and 22-28, and twice weekly during weeks 8, 9, 21 and 21. Stool samples will be compared longitudinally within individual subjects, and between groups.

    Metabolomic evaluation: the relative abundance of metabolites, determined by liquid chromatography-mass spectrometry (LC-MS), will be quantified under each condition and compared between groups.



Secondary Outcome Measures :
  1. Between Phase Relative Abundance of Metabolites and Bacterial Taxa (Efficacy Outcome) [ Time Frame: 28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment) ]

    Within-participant change in the metabolomic profile and targeted metabolites / inflammatory markers after p-inulin treatment compared with pre-treatment

    Metabolomic evaluation: the relative abundance of metabolites, determined by liquid chromatography-mass spectrometry (LC-MS), will be quantified under each condition and compared between groups.

    Microbiota evaluation: the relative abundance of bacterial taxa, as determined by 16S rRNA gene sequencing, will be quantified under each condition and compared between groups.


  2. Within Participant Variability of Bacterial Taxa (Efficacy Outcome) [ Time Frame: 28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment) ]

    Within-participant variability in the bacterial composition of the stool during the no treatment and treatment phases

    Microbiota evaluation: the relative abundance of bacterial taxa, as determined by 16S rRNA gene sequencing, will be quantified.


  3. Between Phase Relative Abundance of Bacterial Taxa (Efficacy Outcome) [ Time Frame: 28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment) ]

    Within-participant change in the bacterial composition of the stool after p-inulin treatment compared with pre-treatment

    Microbiota evaluation: the relative abundance of bacterial taxa, as determined by 16S rRNA gene sequencing, will be quantified.


  4. Relative Abundance of Metabolites Between Diabetic and Non-diabetic Patients (Efficacy Outcome) [ Time Frame: 28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment) ]

    Differences in the overall microbiome composition between diabetic and non-diabetic participants

    Microbiota evaluation: the relative abundance of bacterial taxa, as determined by 16S rRNA gene sequencing, will be quantified under each condition and compared between groups.


  5. Variability of Metabolites and Bacterial Taxa During the No Treatment Phase (Efficacy Outcome) [ Time Frame: 28 weeks ]

    Within-study cohort variability in the metabolomic profile and targeted metabolites / inflammatory markers during the no treatment phase

    Metabolomic evaluation: the relative abundance of metabolites, determined by liquid chromatography-mass spectrometry (LC-MS), will be quantified under each condition and compared between groups.

    Microbiota evaluation: the relative abundance of bacterial taxa, as determined by 16S rRNA gene sequencing, will be quantified under each condition and compared between groups.


  6. Variability of Metabolites and Bacterial Taxa During the Treatment Phase (Efficacy Outcome) [ Time Frame: 12 weeks ]

    Within-study cohort variability in the metabolomic profile and targeted metabolites / inflammatory markers during the p-inulin treatment phase

    Metabolomic evaluation: the relative abundance of metabolites, determined by liquid chromatography-mass spectrometry (LC-MS), will be quantified under each condition and compared between groups.

    Microbiota evaluation: the relative abundance of bacterial taxa, as determined by 16S rRNA gene sequencing, will be quantified under each condition and compared between groups.


  7. Comparison of Variability of Metabolites and Bacterial Taxa During the Treatment/No Treatment Phase (Efficacy Outcome) [ Time Frame: 28 weeks ]

    Within-study cohort variability in the metabolomic profile and targeted metabolites / inflammatory markers after p-inulin treatment compared with pre-treatment

    Metabolomic evaluation: the relative abundance of metabolites, determined by liquid chromatography-mass spectrometry (LC-MS), will be quantified under each condition and compared between groups.

    Microbiota evaluation: the relative abundance of bacterial taxa, as determined by 16S rRNA gene sequencing, will be quantified under each condition and compared between groups.


  8. Change in Score of the Gastrointestinal Symptom Rating Scale (GSRS) (Safety Outcome) [ Time Frame: 28 weeks ]
    -Gastrointestinal symptoms as measured by the Gastrointestinal Symptom Rating Scale (GSRS)

  9. Number of Participants Who Discontinue Use of p-inulin (Tolerability Outcome) [ Time Frame: 12 weeks ]
    -Early discontinuation of p-inulin

  10. Number of Participants Who Reduce the Dose of p-inulin (Tolerability Outcome) [ Time Frame: 12 weeks ]
    -Reduction in p-inulin dose

  11. Number of Participants with Adverse Events (Safety Outcome) [ Time Frame: 28 weeks ]
    -Adverse events per participant related to treatment as coded using the Medical Dictionary for Regulatory Activities (MedDRA) Coding System

  12. Number of Adverse Events (Safety Outcome) [ Time Frame: 28 weeks ]
    -Adverse events categorized by body systems, related to treatment as coded using the Medical Dictionary for Regulatory Activities (MedDRA) Coding System

  13. Rate of Enrollment Refusal (Feasibility Outcome) [ Time Frame: 1 year ]
    Enrollment refusal rate

  14. Stool Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome) [ Time Frame: 28 weeks ]
    Proportion of completed protocol-specified stool sample collections

  15. Blood Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome) [ Time Frame: 28 weeks ]
    Proportion of completed blood sample collections

  16. Adherence Rate of p-inulin Use (Feasibility Outcome) [ Time Frame: 12 weeks ]
    Proportion of p-inulin packets used

  17. Rate of Study Withdrawal (Feasibility Outcome) [ Time Frame: 28 weeks ]
    Number of withdrawals during each phase of the study



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02572882


Locations
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United States, District of Columbia
The George Washington University
Washington, District of Columbia, United States, 20037
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02120
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Washington
Kidney Research Institute, University of Washington
Seattle, Washington, United States, 98104
Sponsors and Collaborators
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Brigham and Women's Hospital
George Washington University
Vanderbilt University
University of Washington
Investigators
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Principal Investigator: Laura Dember, MD University of Pennsylvania
Principal Investigator: J Richard Landis, PhD Perelman School of Medicine at the University of Pennsylvania
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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02572882    
Other Study ID Numbers: 823162
U01DK099919 ( U.S. NIH Grant/Contract )
First Posted: October 9, 2015    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019
Keywords provided by University of Pennsylvania:
hemodialysis
p-inulin
gut microbiome
Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Dysbiosis
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Pathologic Processes