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

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

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