Metabolic Effects, Immunosuppressive Agents, Renal Function, Adverse Events, Gut Microbiome, Flow Cytometry, Immune System, Metabolome
Conditions
Keywords
short chain fatty acids, gut microbiome, kidney transplant recipients
Brief summary
This is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effects of high-dose short-chain fatty acid (SCFA) supplementation on the gut microbiome and host metabolome in stable kidney transplant recipients. Participants will be randomly assigned to receive either 1000 mg of sodium butyrate per day or placebo for a duration of 12 weeks. Comprehensive profiling of the serum and urinary metabolome, along with analysis of the gut microbiome composition and diversity, will be conducted at three time points: baseline, after the intervention period (week 12). The biochemical parameters and the level of tacrolimus will be also examined.
Interventions
DIETARY_SUPPLEMENTSCFA
Participants randomized to this group will receive 1000 mg of sodium butyrate daily for 12 weeks. The intervention aims to evaluate the effect of high-dose SCFA supplementation on the gut microbiome and systemic/urinary metabolome in kidney transplant recipients.
DIETARY_SUPPLEMENTPlacebo
Participants in this group will receive placebo capsules (sacharosis) identical in appearance to the active SCFA capsules, administered twice daily for 12 weeks. This arm serves as a control to evaluate the specific effects of SCFA supplementation.
Sponsors
Comenius University
University Hospital, Martin
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Primary kidney transplantation (living or dead donor) Stable kidney transplant recipients (≥ 6 months post-transplantation) Stable graft function defined as eGFR ≥ 30 mL/min/1.73 m² with no significant change (\>15%) in the last 3 months No episodes of acute rejection within the last 6 months On stable immunosuppressive therapy for at least 3 months Ability to provide written informed consent Willingness and ability to provide stool, urine, and blood samples at specified time points
Exclusion criteria
* Use of antibiotics, probiotics, or prebiotics within 4 weeks prior to enrollment Active gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, celiac disease) Severe intestinal motility disorders or chronic diarrhea Advanced liver disease (Child-Pugh C) Active infection or systemic inflammatory disease requiring treatment Uncontrolled diabetes mellitus (HbA1c \> 9%) Known allergy or intolerance to SCFA or ingredients in the supplement Participation in another interventional clinical trial within the past 30 days Pregnancy or breastfeeding Hospitalization within 30 days prior to enrollment Any condition which, in the opinion of the investigator, may compromise the safety of the participant or the integrity of the study data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in gut microbiome composition after SCFA supplementation | Baseline to Week 12 | Evaluation of gut microbiota diversity and composition (alpha and beta diversity indices, relative abundance of microbial taxa) via 16S rRNA gene sequencing from stool samples. |
| Change in serum and urine metabolomic profile after higehr dose of SCFA supplementation | Baseline to Week 12 | Analysis of systemic metabolic changes using untargeted metabolomic profiling (NMR) in serum and urine samples and comarisation with results in study TNO\_UNM\_SCFA1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of high-dose SCFA supplementation | Baseline to Week 12 | Recording of adverse events (AEs), such as gastrointestinal symptoms. |
| Correlation between gut microbiome composition and serum metabolome. | Baseline to week 12 | Exploratory analysis of correlantion between gut microbiome composition and serum metabolites. |
| Intolerance of high dose SCFA. | Baseline to Week 12. | Recording of treatment discontinuation rates due to intolerance or side effects. |
| correlantion between gut microbiome composition and urinary metabolites | Baseline to week12 | Exploratory analysis of correlantion between gut microbiome composition and urinary metabolites. |
Countries
Slovakia
Outcome results
None listed