TUDCA in High-Risk Lactating Mothers Identified by Early Postpartum Milk Hydrophobicity Index

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Maternal Oral TUDCA in High-Risk Lactating Mother-Infant Dyads Identified by Early Postpartum Breast Milk Bile Acid Hydrophobicity Index

This is a randomized, double-blind, placebo-controlled Phase 2 proof-of-concept trial in mother-infant dyads. The study aims to evaluate the safety, tolerability, and biological effects of maternal oral tauroursodeoxycholic acid (TUDCA) in lactating mothers with metabolic dysfunction-associated steatotic liver disease (MASLD).

Eligible mother-infant dyads will be screened in the early postpartum period using breast milk bile acid hydrophobicity index. Dyads identified as high risk will be randomized 1:1 to maternal oral TUDCA or placebo.

The primary objectives are to assess maternal and infant safety and to evaluate changes in breast milk bile acid hydrophobicity index. Secondary objectives include assessment of infant ketone-related metabolic biomarkers and gut microbiome features. Exploratory outcomes include early infant neurodevelopment during follow-up.

This is a single-center, randomized, double-blind, placebo-controlled Phase 2 interventional study conducted in lactating mother-infant dyads.

Mothers with metabolic dysfunction-associated steatotic liver disease (MASLD) will be screened in the early postpartum period. Breast milk samples collected within the first days after delivery will be analyzed to determine bile acid hydrophobicity index. Dyads meeting a predefined high-risk threshold will be enrolled and randomized in a 1:1 ratio to receive either maternal oral tauroursodeoxycholic acid (TUDCA) or matching placebo.

Study treatment will be administered during the early postpartum period for a defined duration. The primary endpoints include maternal and infant safety and tolerability, as well as changes in breast milk bile acid hydrophobicity index. Secondary endpoints include infant serum beta-hydroxybutyrate levels and gut microbiome features. Exploratory endpoints include early neurodevelopmental outcomes during follow-up.

This study aims to provide proof-of-concept evidence for a mechanism-based intervention targeting maternal milk composition to influence early-life metabolic and developmental pathways.

Inclusion Criteria:

• Lactating mother aged 18 to 45 years
• Within 72 hours after delivery at screening
• Intention to continue breastfeeding or providing expressed breast milk during the treatment period
• Maternal metabolic dysfunction-associated steatotic liver disease (MASLD) defined by protocol-specified clinical criteria
• Early postpartum breast milk sample meeting the predefined high-risk bile acid hydrophobicity index threshold
• Live-born infant considered clinically stable and eligible for enteral feeding
• Ability and willingness to provide written informed consent for maternal participation and infant-related study procedures

Exclusion Criteria:

• Maternal chronic liver disease other than MASLD, decompensated liver disease, biliary obstruction, acute cholecystitis, or pancreatitis
• Current use of ursodeoxycholic acid, tauroursodeoxycholic acid, or another protocol-prohibited bile acid-modifying medication
• Maternal severe renal insufficiency or other clinically significant condition judged by the investigator to increase study risk
• Preterm infant less than 37 weeks of gestation or birth weight less than 2500 g
• Major congenital anomaly or infant condition requiring ongoing intensive care at enrollment
• Any condition that, in the investigator's judgment, makes the mother-infant dyad unsuitable for participation