Probiotic and Prebiotic Supplementation in Peritoneal Dialysis Patients

Official title

Impact of Synbiotic Supplementation in Peritoneal Dialysis Patients

Overview

The goal of this clinical trial is to learn if synbiotics work to lower inflammation in adults with chronic kidney disease who are on peritoneal dialysis. Synbiotics are daily capsules that contain a mix of probiotics (good bacteria) and prebiotics (fiber that feeds good bacteria). The main questions it aims to answer are: Do synbiotics lower the level of inflammation markers in the blood? Do synbiotics improve the nutritional status of the participants? Do synbiotics lower the number of peritonitis (peritoneal infections) episodes? Researchers will compare synbiotics to a placebo to see if the treatment works. A placebo is a look-alike capsule that contains no active ingredients. Participants will: Take 1 capsule every day for 6 months Visit the clinic at the start, at 3 months, and at 6 months for blood tests and nutrition checkups

Detailed description

This is a randomized, controlled, double-blind clinical trial designed to evaluate the clinical and biochemical impact of synbiotic supplementation in patients with chronic kidney disease undergoing peritoneal dialysis at the Regional Center for Kidney Diseases. Eligible participants will be randomly assigned in a 1:1 ratio into one of two parallel groups for a 6-month period:

1. Synbiotic Group: Participants will receive one oral capsule daily in the morning before meals, containing prebiotic fibers (chicory inulin root and tapioca starch) and probiotic strains (Bifidobacterium longum, Lactobacillus acidophilus, and Streptococcus thermophilus) at a concentration of 7.5 x 10\^12 CFU/100g. 2. Placebo Group: Participants will receive one identical, inactive oral capsule daily.

Clinical and biochemical evaluations will be conducted at three distinct time points: Baseline (Visit 1), 3 months (Visit 2), and 6 months (Visit 3). At each visit, blood samples will be drawn to measure primary pro-inflammatory and uremic toxin markers, specifically p-cresol and indoxyl sulfate, alongside high-sensitivity C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Additionally, nutritional status will be evaluated using the Malnutrition-Inflammation Score (MIS). Secondary clinical outcomes, including the incidence of peritonitis episodes, will be documented throughout the entire 6-month study duration. To ensure protocol compliance, participant adherence will be tracked using two methods: Pill-counts conducted during each scheduled follow-up visit and periodic telephone calls between visits to provide reminders and monitor supplement intake.

Interventions

• Dietary supplement Synbiotic
  Oral administration of an active nutritional supplement consisting of one capsule daily taken in the morning before meals for 6 months. Each capsule contains a specific synbiotic formulation composed of probiotic strains (Bifidobacterium longum, Lactobacillus acidophilus, and Streptococcus thermophilus at 7.5 x 10\^12 CFU/100g) combined with prebiotic soluble fibers (chicory inulin root and tapioca starch) designed to modulate the gut microbiota.
• Dietary supplement Placebo
  Oral administration of one identical, inactive oral capsule daily taken in the morning before meals for a period of 6 months. The placebo capsule looks, tastes, and smells exactly like the intervention supplement but contains no active ingredients.

Primary outcome measures

• Change from baseline in serum high-sensitivity C-reactive protein (hs-CRP) at 3 and 6 months. [Time frame: Baseline (Month 0), Month 3, and Month 6.]
• Change from baseline in Erythrocyte Sedimentation Rate (ESR) at 3 and 6 months. [Time frame: Baseline (Month 0), Month 3, and Month 6.]
• Change from baseline in serum p-Cresyl Sulfate (pCS) levels at 3 and 6 months. [Time frame: Baseline (Month 0), Month 3, and Month 6.]
• Change from baseline in serum Indoxyl Sulfate (IS) levels at 3 and 6 months. [Time frame: Baseline (Month 0), Month 3, and Month 6.]

Secondary outcome measures (2)

• Change from baseline in Malnutrition-Inflammation Score (MIS) at 3 and 6 months. [Time frame: Baseline (Month 0), Month 3, and Month 6.]
• Number of peritonitis episodes during the 6-month follow-up period. [Time frame: Up to 6 months.]

Eligibility criteria

Inclusion criteria

• Patients aged 18 years or older.
• Patients diagnosed with kidney disease who have been receiving peritoneal dialysis at home for at least 1 month.

Exclusion criteria

• Patients who are unable to eat or receive food through a feeding tube.
• Patients who have taken prebiotics or probiotics (supplements that support gut health) in the month before the study starts.
• Patients who used antibiotics in the month before the study starts.
• Patients who cannot attend the scheduled follow-up visits (missing the second follow-up appointment will result in being removed from the study).
• Note on non-adherence and withdrawal: Patients who are unable to take their assigned capsules regularly (taking less than 80% of the total capsules will result in being removed from the study).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Supportive care

Study locations

Mexico · 1 center

• Hospital Universitario Dr. José E. González, Centro Regional de Enfermedades Renales (CRER — Monterrey

Publications

• Brown EA, Davies SJ, Rutherford P, Meeus F, Borras M, Riegel W, Divino Filho JC, Vonesh E, van Bree M; EAPOS Group. Survival of functionally anuric patients on automated peritoneal dialysis: the European APD Outcome Study. J Am Soc Nephrol. 2003 Nov;14(11):2948-57. doi: 10.1097/01.asn.0000092146.67909.e2. PMID 14569106
• Liu S, Liu H, Chen L, Liang SS, Shi K, Meng W, Xue J, He Q, Jiang H. Effect of probiotics on the intestinal microbiota of hemodialysis patients: a randomized trial. Eur J Nutr. 2020 Dec;59(8):3755-3766. doi: 10.1007/s00394-020-02207-2. Epub 2020 Feb 28. PMID 32112136
• Sabatino A, Regolisti G, Cosola C, Gesualdo L, Fiaccadori E. Intestinal Microbiota in Type 2 Diabetes and Chronic Kidney Disease. Curr Diab Rep. 2017 Mar;17(3):16. doi: 10.1007/s11892-017-0841-z. PMID 28271466
• Arteaga-Muller GY, Flores-Trevino S, Bocanegra-Ibarias P, Robles-Espino D, Garza-Gonzalez E, Fabela-Valdez GC, Camacho-Ortiz A. Changes in the Progression of Chronic Kidney Disease in Patients Undergoing Fecal Microbiota Transplantation. Nutrients. 2024 Apr 10;16(8):1109. doi: 10.3390/nu16081109. PMID 38674803
• Tian N, Li L, Ng JK, Li PK. The Potential Benefits and Controversies of Probiotics Use in Patients at Different Stages of Chronic Kidney Disease. Nutrients. 2022 Sep 29;14(19):4044. doi: 10.3390/nu14194044. PMID 36235699
• Lim YJ, Sidor NA, Tonial NC, Che A, Urquhart BL. Uremic Toxins in the Progression of Chronic Kidney Disease and Cardiovascular Disease: Mechanisms and Therapeutic Targets. Toxins (Basel). 2021 Feb 13;13(2):142. doi: 10.3390/toxins13020142. PMID 33668632
• Andreoli MCC, Totoli C. Peritoneal Dialysis. Rev Assoc Med Bras (1992). 2020 Jan 13;66Suppl 1(Suppl 1):s37-s44. doi: 10.1590/1806-9282.66.S1.37. PMID 31939534
• Wieers G, Belkhir L, Enaud R, Leclercq S, Philippart de Foy JM, Dequenne I, de Timary P, Cani PD. How Probiotics Affect the Microbiota. Front Cell Infect Microbiol. 2020 Jan 15;9:454. doi: 10.3389/fcimb.2019.00454. eCollection 2019. PMID 32010640

Identifiers

NCT: NCT07694791 · NF25-00008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗