Gut Microbiome and p-Inulin in CKD TarGut CKD Study
Trial Snapshot
- Phase
- Not Applicable
- Enrollment
- 18
- Locations
- 2
- Primary Endpoint
- Microbial composition of stool
Study Overview
Brief Summary
The purpose of this Phase 1, 3-period crossover with repeated measures feasibility study is to characterize the gut microbiome of individuals with chronic kidney disease, and to explore effects of p-inulin on the gut microbiome. The nature of the study will provide information about the feasibility of stool sample collection for future multicenter studies of the gut microbiome.
Detailed Description
The overarching hypothesis motivating this exploratory study of variability is that treatment with oligofructose-enriched inulin (p-inulin) will alter the composition and/or function of the gut microbiome, and thereby reduce the generation of gut-derived uremic toxins, improve gut barrier function and attenuate systemic inflammation in CKD patients. In order to design a future clinical trial the following parameters from CKD subjects are needed:
- Intra-patient variability in the composition and function of the gut microbiome
- Inter-patient variability in the composition and function of the gut microbiome
- Impact of p-inulin on the composition and function of the gut microbiome
- Tolerability of p-inulin administration
- Feasibility of collecting stool samples in this patient population
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects with eGFR 15.0 to 50.0 ml/min/1.73 m2 as estimated by the CKD-EPI equation
- •Albuminuria greater than 300 mg/g creatinine (by spot urine test) if eGFR is ≥45 ml/min/1.73 m2
- •Age ≥ 18 years
- •For women of childbearing potential, willingness to use a highly effective method of birth control for up to 4 weeks after the last dose to study drug. See Section 4.2.1 for definition of childbearing potential and acceptable methods of birth control
- •Ability to provide informed consent
Exclusion Criteria
- •Use of pre- or pro-biotics during the past 2 months
- •Consumption of probiotic yogurt during the past 2 weeks
- •Use of antibiotics within the past 3 months if the patient received a single course of antibiotic. If the patient received more than one course of antibiotic treatment, we will wait for 6 months prior to inclusion.
- •Presence of HIV infection, chronic wound infection and osteomyelitis
- •Presence of or treatment for periodontal infection
- •Inflammatory bowel disease, chronic diarrhea, current C. difficile infection
- •Cirrhosis or chronic active hepatitis
- •Treatment with immunosuppressive medications in the past 6 months or more than a week of treatment with prednisone >10 mg in the last 3 months
- •Treatment with proton pump inhibitors within the last one month
- •Anticipated initiation of dialysis or kidney transplant within 9 months
- •Acute on chronic kidney disease
- •Expected survival < 9 months Do not disclose or use except as authorized by the Pilot Clinical Trials in CKD Consortium.
- •Pregnancy, anticipated pregnancy, or breastfeeding
- •Incarceration
- •Participation in another intervention study
- •Severe anemia defined as hemoglobin <9.0 g/dl any time during the last 3 months
- •Patients in whom frequent blood sampling may be difficult
Arms & Interventions
Oligofructose-enriched inulin (p-inulin)
Participants are on no treatment for 8 weeks, then the pre-biotic p-inulin for 12 weeks, then no treatment for 8 weeks. Inulin is derived from chicory root fiber. The dose is 16 grams of p-inulin powder per day.
Intervention: Oligofructose-enriched inulin (p-inulin) (Dietary Supplement)
Oligofructose-enriched inulin (p-inulin)
Participants are on no treatment for 8 weeks, then the pre-biotic p-inulin for 12 weeks, then no treatment for 8 weeks. Inulin is derived from chicory root fiber. The dose is 16 grams of p-inulin powder per day.
Intervention: No treatment (Other)
Outcomes
Primary Outcomes
Microbial composition of stool
Time Frame: Stool is collected weekly for 28 weeks
Microbial taxonomy will be assigned using Ribosomal Database Project (RDP) for 16S, augmented by analysis of specific sequences using BLAST. The 16S tag sequences will be collected into operational taxonomic units (OTUs) with 97% sequence identity.
Adherence to p inulin prescription
Time Frame: Packets are counted every four weeks during the 12 weeks when the patient is taking p inulin
Proportion of packets taken vs packets prescribed by packet count
Secondary Outcomes
- Allantoin(collected weekly for 28 weeks)
- Indoles(collected weekly for 28 weeks)
- Phenols(collected weekly for 28 weeks)
- Fructose(collected weekly for 28 weeks)
- Cytokines(collected weekly for 28 weeks)
- endotoxin(collected weekly for 28 weeks)
- TNF-R1(collected weekly for 28 weeks)
- Lipopolysaccharide binding protein (LBP)(collected weekly for 28 weeks)
- sCD14(collected weekly for 28 weeks)
- butyrate(Collected weekly for 28 weeks)
- Choline(Collected weekly for 28 weeks)
- Betaine(Collected weekly for 28 weeks)
- metabolites of urea and creatinine metabolism(collected weekly for 28 weeks)
- Myeloperoxdase (MPO)(collected weekly for 28 weeks)
- HMGB1(collected weekly for 28 weeks)
- propionate(Collected weekly for 28 weeks)
- acetate(Collected weekly for 28 weeks)
- Trimethylamine N oxide(Collected weekly for 28 weeks)
- polyamines(collected weekly for 28 weeks)
- hsCRP(collected weekly for 28 weeks)
- TNF-R2(collected weekly for 28 weeks)
Investigators
Jennifer Gassman
Principal Investigator - Data Coordinating Center
The Cleveland Clinic