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

Chronic Kidney Diseases Clinical Trial

— TarGut  

Official title:

Gut Microbiome and p-Inulin in CKD TarGut CKD Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03348592
• Other study ID #: DK099877-T
• Status: Active, not recruiting
• Phase: N/A
• First received: October 31, 2017
• Last updated: November 15, 2017
• Start date: October 2016
• Est. completion date: June 2018

Study information

• Verified date: November 2017
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: June 2018
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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.

Locations

Country	Name	City	State
United States	The George Washington University Medical Faculty Associates	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	George Washington University, University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	butyrate	captured by untargeted metabolomics, short chain fatty acid in stool blood and urine	Collected weekly for 28 weeks
Secondary	propionate	captured by untargeted metabolomics, short chain fatty acid in stool blood and urine	Collected weekly for 28 weeks
Secondary	acetate	captured by untargeted metabolomics, short chain fatty acid measured in stool blood and urine	Collected weekly for 28 weeks
Secondary	Trimethylamine N oxide	captured by untargeted metabolomics in stool blood and urine	Collected weekly for 28 weeks
Secondary	Choline	captured by untargeted metabolomics in stool blood and urine	Collected weekly for 28 weeks
Secondary	Betaine	captured by untargeted metabolomics in stool blood and urine	Collected weekly for 28 weeks
Secondary	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
Secondary	Phenols	p-cresol sulfate p-Cresol glucuronide Phenyl sulfate Phenyl glucuronide a-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
Secondary	polyamines	captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
Secondary	metabolites of urea and creatinine metabolism	captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
Secondary	Allantoin	captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
Secondary	Fructose	captured by untargeted metabolomics in stool blood and urine	collected weekly for 28 weeks
Secondary	Cytokines	IL-1ß IL-2 IL-4 IL-6 IL-10 IL-17 IL-22 TNFa measured by standard ELISA in stool	collected weekly for 28 weeks
Secondary	endotoxin	measured by standard ELISA in stool	collected weekly for 28 weeks
Secondary	Myeloperoxdase (MPO)	measured by standard ELISA in stool	collected weekly for 28 weeks
Secondary	hsCRP	measured by standard ELISA in stool	collected weekly for 28 weeks
Secondary	HMGB1	measured by standard ELISA in stool	collected weekly for 28 weeks
Secondary	TNF-R1	measured by standard ELISA in stool	collected weekly for 28 weeks
Secondary	TNF-R2	measured by standard ELISA in stool	collected weekly for 28 weeks
Secondary	Lipopolysaccharide binding protein (LBP)	measured by standard ELISA in stool	collected weekly for 28 weeks
Secondary	sCD14	measured by standard ELISA in stool	collected weekly for 28 weeks