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

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.

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