Metabolic Dysfunction-Associated Steatotic Liver Disease Infant Development
Conditions
Keywords
TUDCA, tauroursodeoxycholic acid, breast milk bile acids, hydrophobicity index, beta-hydroxybutyrate, gut microbiome, mother-infant dyad, MASLD, neurodevelopment
Brief summary
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.
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.
Interventions
Maternal oral tauroursodeoxycholic acid administered according to the protocol-defined dose and schedule during the early postpartum period.
DRUGPlacebo
Matching maternal oral placebo administered according to the same schedule as the experimental arm during the early postpartum period.
Sponsors
Peking University First Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, care providers, investigators, and outcome assessors will remain blinded to treatment assignment. Maternal oral TUDCA and placebo will be matched in appearance, packaging, and administration schedule. The randomization code will be maintained by authorized unblinded pharmacy or study personnel and will not be released until database lock unless medically necessary for participant safety.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of maternal treatment-emergent adverse events | Baseline to Day 28 | Number of lactating mothers with treatment-emergent adverse events, serious adverse events, treatment discontinuation, or clinically significant safety findings during the study period. |
| Incidence of infant treatment-emergent adverse events | Birth to Day 28 | 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. |
| Change in breast milk bile acid hydrophobicity index | Baseline to Day 7 | Change from baseline in breast milk bile acid hydrophobicity index measured by targeted liquid chromatography-mass spectrometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infant serum beta-hydroxybutyrate concentration | Day 7 and Day 14 | Infant serum beta-hydroxybutyrate concentration measured during follow-up. |
| Infant stool microbiome features | Day 7 and Day 14 | Changes in infant stool microbiome composition and predefined microbial features during follow-up. |
| Breast milk bile acid composition | Baseline, Day 7, and Day 14 | Breast milk bile acid composition measured using targeted metabolomic profiling. |
| Early infant neurodevelopmental screening score | 3 months after birth | Exploratory early infant neurodevelopmental assessment using a protocol-defined developmental screening tool. |
Contacts
CONTACTYuhang Zhang
PRINCIPAL_INVESTIGATORYuhang Zhang, MD, PhD
Peking University First Hospital
Outcome results
None listed