TUDCA in High-Risk Lactating Mothers Identified by Early Postpartum Milk Hydrophobicity Index (MILK-HI-TUDCA)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease Infant Development
• Intervention / Treatment: Drug: tauroursodeoxycholic acid (TUDCA); Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yuhang Zhang; Phone Number: 86-010-83950400; Email: yuhang@pkufh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maternal Oral TUDCA; High-risk mother-infant dyads randomized to this arm will receive maternal oral tauroursodeoxycholic acid (TUDCA) during the early postpartum period in addition to standard postpartum care and breastfeeding support.	Drug: tauroursodeoxycholic acid (TUDCA); Maternal oral tauroursodeoxycholic acid administered according to the protocol-defined dose and schedule during the early postpartum period.; Other Names: TUDCA
Placebo Comparator: Maternal Oral Placebo; High-risk mother-infant dyads randomized to this arm will receive matching maternal oral placebo during the early postpartum period in addition to standard postpartum care and breastfeeding support.	Drug: Placebo; Matching maternal oral placebo administered according to the same schedule as the experimental arm during the early postpartum period.; Other Names: Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of maternal treatment-emergent adverse events	Number of lactating mothers with treatment-emergent adverse events, serious adverse events, treatment discontinuation, or clinically significant safety findings during the study period.	Baseline to Day 28
Incidence of infant treatment-emergent adverse events	Number of infants with clinically significant adverse events, feeding intolerance, vomiting, diarrhea, jaundice requiring treatment, hospitalization, or other protocol-defined safety events during follow-up.	Birth to Day 28
Change in breast milk bile acid hydrophobicity index	Change from baseline in breast milk bile acid hydrophobicity index measured by targeted liquid chromatography-mass spectrometry.	Baseline to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant serum beta-hydroxybutyrate concentration	Infant serum beta-hydroxybutyrate concentration measured during follow-up.	Day 7 and Day 14
Infant stool microbiome features	Changes in infant stool microbiome composition and predefined microbial features during follow-up.	Day 7 and Day 14
Breast milk bile acid composition	Breast milk bile acid composition measured using targeted metabolomic profiling.	Baseline, Day 7, and Day 14
Early infant neurodevelopmental screening score	Exploratory early infant neurodevelopmental assessment using a protocol-defined developmental screening tool.	3 months after birth

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Principal Investigator: Yuhang Zhang, MD, PhD, Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 2, 2026
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: gut microbiome; neurodevelopment; TUDCA; beta-hydroxybutyrate; tauroursodeoxycholic acid; mother-infant dyad; MASLD; breast milk bile acids; hydrophobicity index
• Additional Relevant MeSH Terms: ursodoxicoltaurine
• Other Study ID Numbers: PKUFH-MASLD-MILKHI-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No