Modulazione della Composizione del Microbiota Intestinale e dei Profili di Permeabilità Intestinale mediante Integrazione con Simbiotico Multispecie in Pazienti in Emodialisi

Study Design and Objectives

This investigation is a single-arm, open-label pilot trial designed to assess the impact of a multispecies synbiotic supplementation on gut-derived uremic toxins and fecal microbiota composition over 12 weeks in adults with in a group of hemodialysis patients.

The primary objectives are to:

• Evaluate changes in fecal microbiomes,
• Assess the serum levels of uremic toxins and gut permeability markers

Study Population

• Inclusion criteria: Adults aged 18 years or older receiving maintenance hemodialysis patients for at least 3 months
• Exclusion criteria:
• Use of probiotic supplements within the last month;
• Hospitalization within the past month for acute infections or CKD-related complications;
• History of major intestinal surgeries (gastrectomy, cholecystectomy; appendectomy allowed);
• Presence of viral hepatitis, liver cirrhosis, active malignancy, advanced congestive heart failure, or thyroid disorders;
• Use of antibiotics or immunosuppressive therapy within the preceding three months.

Sample Size Justification This pilot study targets 30 participants, which provides adequate power (80%, alpha 0.05) to detect a medium effect size (Cohen's d = 0.6) on the primary outcome, serum indoxyl sulfate levels. Calculations based on expected changes from 8.0 mg/L to 6.5 mg/L with SD of 2.5 mg/L indicate a required sample size of ~24; the sample size accounts for potential dropouts to ensure study robustness.

Study Procedures

• Baseline assessments:
• Measurement of serum and urine uremic toxins,
• Measurement of gut permeability markers
• Fecal microbiome analysis
• Intervention:

Participants will receive Renobiome multispecies synbiotic containing 30 billion CFUs per capsule, including strains of Lactobacillus salivarius LS 159, Lactobacillus pentosus LPE 588, and Lactococcus lactis LL 358 with additional prebiotics

• Dose: One capsule twice daily (morning and evening), with or without food, taken with room-temperature water.
• Storage: Capsules to be kept below 25°C, in a dry, light-protected environment.
• Follow-up and Monitoring:
• At 4 weeks: Monitoring and documentation of gastrointestinal symptoms and adverse events.
• At 12 weeks: Repeat evaluations identical to baseline, including blood and urine tests.

Compliance and Safety

• Adherence will be tracked via regular follow-up contacts.
• An adherence rate of 80-100% is considered acceptable.
• All adverse drug reactions and any unexpected events will be recorded throughout the study duration.

Biological Sample Collection and Laboratory Methods

• Blood Sampling:
• Fasting blood samples will be collected following an 8-hour fast.
• Samples will be centrifuged at 3,000 rpm for 10 minutes within 1 hour post-collection.
• Serum aliquots (200 μL) will be stored at -80°C until batch analysis.
• Intestinal permeability markers: Intestinal fatty acid-binding protein (I-FABP), diamine oxidase (DAO),and zonulin (human)
• Concentrations of indoxyl sulfate (IS), p-cresyl sulfate (PCS), indole acetic acid (IAA), and indolelactic acid (ILA) in serum and urine will be determined by high-performance liquid chromatography (HPLC) according to established protocols.
• Fecal microbiome analysis

Ethical Considerations

• Written informed consent will be obtained from all participants before enrollment.
• The study will be conducted in compliance with Taiwanese Good Clinical Practice (GCP) guidelines, local regulatory requirements, and the Declaration of Helsinki.
• Ethical approval has been granted by the Institutional Review Board of Tungs' Taichung MetroHarbour Hospital.