Clinical trial NCT02572882: 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
Overall status: COMPLETED
Phase: NA
Conditions: End-Stage Renal Disease
Gut Microbiome Dysbiosis
Keywords: hemodialysis
p-inulin
gut microbiome
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Brigham and Women's Hospital
name: George Washington University
name: Vanderbilt University
name: University of Washington
First posted: 2015-10-09
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Within Participant Variability in Microbiome Composition by Treatment Phase
timeFrame: 28 weeks
measure: Within Participant Variability in Stool Metabolome by Treatment Phase
timeFrame: 28 weeks
measure: Within Participant Variability in Plasma Metabolome by Treatment Phase
timeFrame: 28 weeks (8 weeks pre-treatment, 12 weeks of treatment, 8 weeks post-treatment)
Secondary outcomes:
measure: Change in Score of Gastrointestinal Symptom Rating Scale (GSRS) (Safety Outcome)
timeFrame: GSRS was assessed at Weeks 0, 4, 8, 12, 16, 20, 24 and 28.
measure: Number of Participants Who Discontinued Use of P-inulin (Tolerability Outcome)
timeFrame: 12 weeks
measure: Number of Participants Who Reduce the Dose of P-inulin (Tolerability Outcome)
timeFrame: 12 weeks
measure: Number of Participants With Adverse Events (Safety Outcome)
timeFrame: 28 weeks
measure: Number of Serious Adverse Events (Safety Outcome)
timeFrame: 28 weeks
measure: Rate of Enrollment Refusal (Feasibility Outcome)
timeFrame: 1 year
measure: Stool Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)
timeFrame: 28 weeks
measure: Blood Specimen Collection Proportion - Protocol Adherence (Feasibility Outcome)
timeFrame: 28 weeks
measure: Adherence Rate of P-inulin Use (Feasibility Outcome)
timeFrame: 12 weeks
measure: Rate of Study Withdrawal (Feasibility Outcome)
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Washington
country: United States
facility: The George Washington University
state: District of Columbia
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Seattle
country: United States
facility: Kidney Research Institute, University of Washington
state: Washington
Study officials:
affiliation: University of Pennsylvania
name: Laura Dember, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Perelman School of Medicine at the University of Pennsylvania
name: J Richard Landis, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.