Gut Microbiome and p-Inulin in CKD - TarGut CKD Study (TarGut)

Gut Microbiome and p-Inulin in CKD TarGut CKD Study

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Dietary supplement: Oligofructose-enriched inulin (p-inulin); Other: No treatment

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:

1. Intra-patient variability in the composition and function of the gut microbiome
2. Inter-patient variability in the composition and function of the gut microbiome
3. Impact of p-inulin on the composition and function of the gut microbiome
4. Tolerability of p-inulin administration
5. Feasibility of collecting stool samples in this patient population

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The George Washington University Medical Faculty Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects with eGFR 15.0 to 50.0 ml/min/1.73 m2 as estimated by the CKD-EPI equation
2. Albuminuria greater than 300 mg/g creatinine (by spot urine test) if eGFR is ≥45 ml/min/1.73 m2
3. Age ≥ 18 years
4. 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
5. Ability to provide informed consent

Exclusion Criteria:

1. Use of pre- or pro-biotics during the past 2 months
2. Consumption of probiotic yogurt during the past 2 weeks
3. 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.
4. Presence of HIV infection, chronic wound infection and osteomyelitis
5. Presence of or treatment for periodontal infection
6. Inflammatory bowel disease, chronic diarrhea, current C. difficile infection
7. Cirrhosis or chronic active hepatitis
8. 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
9. Treatment with proton pump inhibitors within the last one month
10. Anticipated initiation of dialysis or kidney transplant within 9 months
11. Acute on chronic kidney disease
12. Expected survival < 9 months Do not disclose or use except as authorized by the Pilot Clinical Trials in CKD Consortium.
13. Pregnancy, anticipated pregnancy, or breastfeeding
14. Incarceration
15. Participation in another intervention study
16. Severe anemia defined as hemoglobin <9.0 g/dl any time during the last 3 months
17. Patients in whom frequent blood sampling may be difficult

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Dietary supplement: Oligofructose-enriched inulin (p-inulin); Other: No treatment; Patients do not take a supplement during the first 8 weeks or the last 8 weeks of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbial composition of stool	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.	Stool is collected weekly for 28 weeks
Adherence to p inulin prescription	Proportion of packets taken vs packets prescribed by packet count	Packets are counted every four weeks during the 12 weeks when the patient is taking p inulin

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
butyrate	captured by untargeted metabolomics, short chain fatty acid in stool blood and urine	Collected weekly for 28 weeks
propionate	captured by untargeted metabolomics, short chain fatty acid in stool blood and urine	Collected weekly for 28 weeks
acetate	captured by untargeted metabolomics, short chain fatty acid measured in stool blood and urine	Collected weekly for 28 weeks
Trimethylamine N oxide	captured by untargeted metabolomics in stool blood and urine	Collected weekly for 28 weeks
Choline	captured by untargeted metabolomics in stool blood and urine	Collected weekly for 28 weeks
Betaine	captured by untargeted metabolomics in stool blood and urine	Collected weekly for 28 weeks
Indoles	Indoxyl sulfate Indoxyl glucuronide 5-hydroxyindole Indole-3-prioonic acid Indole-3-acetic acid captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
Phenols	p-cresol sulfate p-Cresol glucuronide Phenyl sulfate Phenyl glucuronide α-N-phenylacetyl-L-glutamine Phenylpropionylglycine Hippuric acid 4-hydroxybenzoate Phenylacetylglycine * captured by untargeted metabolomics and quantitated by targeted metabolomics in stool blood urine	collected weekly for 28 weeks
polyamines	captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
metabolites of urea and creatinine metabolism	captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
Allantoin	captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
Fructose	captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
Cytokines	IL-1β IL-2 IL-4 IL-6 IL-10 IL-17 IL-22 TNFα measured by standard ELISA in stool	collected weekly for 28 weeks
endotoxin	measured by standard ELISA in stool	collected weekly for 28 weeks
Myeloperoxdase (MPO)	measured by standard ELISA in stool	collected weekly for 28 weeks
hsCRP	measured by standard ELISA in stool	collected weekly for 28 weeks
HMGB1	measured by standard ELISA in stool	collected weekly for 28 weeks
TNF-R1	measured by standard ELISA in stool	collected weekly for 28 weeks
TNF-R2	measured by standard ELISA in stool	collected weekly for 28 weeks
Lipopolysaccharide binding protein (LBP)	measured by standard ELISA in stool	collected weekly for 28 weeks
sCD14	measured by standard ELISA in stool	collected weekly for 28 weeks

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: University of Pennsylvania; George Washington University
• Investigators: Study Director: Kevin C. Abbott, MD, MPH, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Principal Investigator: Jennifer J. Gassman, Ph.D., The Cleveland Clinic; Study Chair: Linda F. Fried, MD, MPH, VA Pittsburgh Healthcare System

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): November 1, 2017
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: November 15, 2017
• First Posted (Actual): November 21, 2017

Study Record Updates

• Last Update Posted (Actual): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Microbiome, p-inulin
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: DK099877-T