MIMIGA Study
Title:
Modification of Intestinal Microbiome in Patients with Primary IgA Nephropathy (IgAN)
Objective:
To evaluate whether supplementation with short-chain fatty acids (SCFAs)-specifically sodium butyrate-can reduce proteinuria and slow the progression of chronic kidney disease (CKD) in patients with IgAN by modulating the gut microbiome.
Study Design:
Type: Randomized, double-blind, placebo-controlled, crossover clinical trial.
Participants: Adults with biopsy-proven IgA nephropathy and matched healthy controls.
Phases:
Treatment Period 1: 12 weeks of SCFA or placebo.
Washout Period: 12 weeks.
Treatment Period 2: Crossover-those who received SCFA get placebo and vice versa for 24 weeks.
Follow-up: 4-8 weeks post-treatment.
Primary Endpoint:
≥25% reduction in proteinuria (urinary protein-creatinine ratio) from baseline at week 12 and 24.
Secondary and Exploratory Endpoints:
Changes in:
eGFR (kidney function)
Inflammatory cytokines (IL-1, IL-6, IL-10, TNF-α)
Gut microbiome composition (via 16S rRNA sequencing)
Progression to CKD stage 4
Systolic blood pressure
Serum lipids
Quality of life (KDQOL-36 questionnaire)
Safety Monitoring:
Adverse events, especially gastrointestinal issues.
Blood and urine biochemistry.
Clinical symptoms and patient-reported outcomes.
Eligibility Criteria:
Inclusion: Adults with IgAN, stable on RAS inhibitors, eGFR ≥ 30 ml/min/1.73 m².
Exclusion: Diabetes, other kidney or autoimmune diseases, recent use of immunosuppressants or antibiotics, uncontrolled hypertension, liver disease, pregnancy.
Microbiome Analysis:
DNA from stool samples analyzed using next-generation sequencing (NGS) targeting the V3-V4 regions of the 16S rRNA gene.
Expected Impact:
Provide first clinical evidence for SCFA as a safe, cost-effective therapy to slow CKD progression in IgAN.
Open new research directions for gut microbiome-targeted treatments in nephrology and other fields (e.g., diabetes, immunology).
Inclusion Criteria:
Inclusion Criteria for SGLT2i stable subjects
Exclusion Criteria:
current diagnosis with another chronic kidney disease, including diabetic kidney disease,secondary IgAN, type 1 or 2 diabetes mellitus
gastrointestinal diseases (such as IBD, peptic ulcers etc.),
another immunological or autoimmune disorders
alcohol abuse
psychiatric disease and inability to assess follow-up
+history of kidney transplantation or another organ transplantation,
use of systemic immunosuppressant medications, such as steroids, in the past 3 months, use of ATB in the past three months
blood pressure above 150 mmHg systolic or 95 mmHg diastolic
clinically significant history of liver disease (aspartate transaminase [AST] or alanine ttransaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
For women - pregnancy, breastfeeding, or intent to become pregnant during the study
For men - intent to father a child or donate sperm during the study
If the patient has received any investigational agent or approved treatment for IgAN (other than a RAS inhibitor) within one month (or five half-lives of the agent, whichever is longer) prior to Screening, if the investigational agent is a cytotoxic or mmunosuppressive, then this washout period is six months
Participants in this arm will: First receive SCFA (sodium butyrate) 400 mg once daily for 12 weeks (Treatment Period 1) Undergo a 12-week washout period Then switch to placebo for 24 weeks (Treatment Period 2)
Participants in this arm will: First receive placebo for 12 weeks (Treatment Period 1) Undergo a 12-week washout period Then switch to SCFA (sodium butyrate) 400 mg once daily for 24 weeks (Treatment Period 2)
Martin, 036 01, Slovakia
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