Back to resultsGut Microbiome and p-Inulin in CKD - TarGut CKD Study (TarGut)
Primary Purpose
Chronic Kidney Diseases
Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Oligofructose-enriched inulin (p-inulin)
No treatment
Sponsored by
About this trial
This is an interventional basic science trial for Chronic Kidney Diseases focused on measuring Microbiome, p-inulin
Eligibility Criteria
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
Sites / Locations
- The George Washington University Medical Faculty Associates
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Oligofructose-enriched inulin (p-inulin)
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Adherence to p inulin prescription
Proportion of packets taken vs packets prescribed by packet count
Secondary Outcome Measures
butyrate
captured by untargeted metabolomics, short chain fatty acid in stool blood and urine
propionate
captured by untargeted metabolomics, short chain fatty acid in stool blood and urine
acetate
captured by untargeted metabolomics, short chain fatty acid measured in stool blood and urine
Trimethylamine N oxide
captured by untargeted metabolomics in stool blood and urine
Choline
captured by untargeted metabolomics in stool blood and urine
Betaine
captured by untargeted metabolomics in stool blood and urine
Indoles
Indoxyl sulfate Indoxyl glucuronide 5-hydroxyindole Indole-3-prioonic acid Indole-3-acetic acid captured by untargeted metabolomics in stool blood and urine
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
polyamines
captured by untargeted metabolomics in stool blood and urine
metabolites of urea and creatinine metabolism
captured by untargeted metabolomics in stool blood and urine
Allantoin
captured by untargeted metabolomics in stool blood and urine
Fructose
captured by untargeted metabolomics in stool blood and urine
Cytokines
IL-1β IL-2 IL-4 IL-6 IL-10 IL-17 IL-22 TNFα measured by standard ELISA in stool
endotoxin
measured by standard ELISA in stool
Myeloperoxdase (MPO)
measured by standard ELISA in stool
hsCRP
measured by standard ELISA in stool
HMGB1
measured by standard ELISA in stool
TNF-R1
measured by standard ELISA in stool
TNF-R2
measured by standard ELISA in stool
Lipopolysaccharide binding protein (LBP)
measured by standard ELISA in stool
sCD14
measured by standard ELISA in stool
Full Information
NCT ID
NCT03348592
First Posted
October 31, 2017
Last Updated
November 15, 2017
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
George Washington University, University of Pennsylvania
1. Study Identification
Unique Protocol Identification Number
NCT03348592
Brief Title
Gut Microbiome and p-Inulin in CKD - TarGut CKD Study
Acronym
TarGut
Official Title
Gut Microbiome and p-Inulin in CKD TarGut CKD Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Unknown status
Study Start Date
October 2016 (Actual)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
June 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators
George Washington University, University of Pennsylvania
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Diseases
Keywords
Microbiome, p-inulin
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
This is a 28 week study. Participants take no treatment for 8 weeks, followed by 12 weeks on the pre-biotic p-inulin, followed by no treatment for 8 weeks. The treatment arms are no treatment and the pre-biotic p-inulin. Inulin is derived from chicory root fiber.
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Oligofructose-enriched inulin (p-inulin)
Arm Type
Experimental
Arm Description
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 Type
Dietary Supplement
Intervention Name(s)
Oligofructose-enriched inulin (p-inulin)
Intervention Type
Other
Intervention Name(s)
No treatment
Intervention Description
Patients do not take a supplement during the first 8 weeks or the last 8 weeks of the study.
Primary Outcome Measure Information:
Title
Microbial composition of stool
Description
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.
Time Frame
Stool is collected weekly for 28 weeks
Title
Adherence to p inulin prescription
Description
Proportion of packets taken vs packets prescribed by packet count
Time Frame
Packets are counted every four weeks during the 12 weeks when the patient is taking p inulin
Secondary Outcome Measure Information:
Title
butyrate
Description
captured by untargeted metabolomics, short chain fatty acid in stool blood and urine
Time Frame
Collected weekly for 28 weeks
Title
propionate
Description
captured by untargeted metabolomics, short chain fatty acid in stool blood and urine
Time Frame
Collected weekly for 28 weeks
Title
acetate
Description
captured by untargeted metabolomics, short chain fatty acid measured in stool blood and urine
Time Frame
Collected weekly for 28 weeks
Title
Trimethylamine N oxide
Description
captured by untargeted metabolomics in stool blood and urine
Time Frame
Collected weekly for 28 weeks
Title
Choline
Description
captured by untargeted metabolomics in stool blood and urine
Time Frame
Collected weekly for 28 weeks
Title
Betaine
Description
captured by untargeted metabolomics in stool blood and urine
Time Frame
Collected weekly for 28 weeks
Title
Indoles
Description
Indoxyl sulfate Indoxyl glucuronide 5-hydroxyindole Indole-3-prioonic acid Indole-3-acetic acid captured by untargeted metabolomics in stool blood and urine
Time Frame
collected weekly for 28 weeks
Title
Phenols
Description
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
Time Frame
collected weekly for 28 weeks
Title
polyamines
Description
captured by untargeted metabolomics in stool blood and urine
Time Frame
collected weekly for 28 weeks
Title
metabolites of urea and creatinine metabolism
Description
captured by untargeted metabolomics in stool blood and urine
Time Frame
collected weekly for 28 weeks
Title
Allantoin
Description
captured by untargeted metabolomics in stool blood and urine
Time Frame
collected weekly for 28 weeks
Title
Fructose
Description
captured by untargeted metabolomics in stool blood and urine
Time Frame
collected weekly for 28 weeks
Title
Cytokines
Description
IL-1β IL-2 IL-4 IL-6 IL-10 IL-17 IL-22 TNFα measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
Title
endotoxin
Description
measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
Title
Myeloperoxdase (MPO)
Description
measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
Title
hsCRP
Description
measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
Title
HMGB1
Description
measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
Title
TNF-R1
Description
measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
Title
TNF-R2
Description
measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
Title
Lipopolysaccharide binding protein (LBP)
Description
measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
Title
sCD14
Description
measured by standard ELISA in stool
Time Frame
collected weekly for 28 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin C. Abbott, MD, MPH
Organizational Affiliation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Jennifer J. Gassman, Ph.D.
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Linda F. Fried, MD, MPH
Organizational Affiliation
VA Pittsburgh Healthcare System
Official's Role
Study Chair
Facility Information:
Facility Name
The George Washington University Medical Faculty Associates
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Gut Microbiome and p-Inulin in CKD - TarGut CKD Study
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