Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease

Ulcerative Colitis Clinical Trial

Official title: Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease

Status Active, not recruiting

Clinical Trial Summary

Breastfeeding is beneficial to both mother and baby. However, many breastfeeding women are affected by long-term health conditions and need to take medications. Sometimes, concerns about transfer of drugs to infants via breast milk lead the mothers to either avoid breastfeeding or stop their medication.

Inflammatory Bowel Disease (IBD) is a chronic condition that is marked by an abnormal response of the body's immune system, and high levels of certain proteins that cause inflammation (Cytokines like Tumor Necrosis Factor-alpha or TNFα). A group of drugs called "biologics" target and stop these proteins from causing inflammation, and have been successfully used to treat this condition. Inflammatory proteins may be present in breast milk of healthy women in variable levels, and may play a role in development of infant's brain and immune system.

This study is being conducted to investigate:

• Concentration of some of the inflammatory proteins in breast milk of mothers with IBD and healthy controls

• Interaction between these proteins and biologics in breast milk of women with IBD

• Potential role of these proteins (and their interaction with biologics) on development of infant learning and memory function It has been presumed that concentrations of TNFα and some other cytokines are higher in breast milk of women with IBD, and the biologics can normalize these high levels.

Due to precautions for COVID-19, the study now consists of only two mandatory study visits and two optional study visits. The mandatory visits include two home visits in the first 4 months postpartum to complete a participant questionnaire and collect a small sample of breast milk at each visit. The optional study visits consist of two visits at the Hospital for Sick Children for evaluation of learning and memory function of the infant at the ages of 12 and 18 months. Additionally, mothers will be required to complete for their infant subscales of The Ages and Stages Questionnaires®, Third Edition (ASQ®-3) either in person or over the telephone at the ages of 12 months and 18 months.

Clinical Trial Description

The inflammatory bowel disease (IBD) shows the highest incidence among people of childbearing age. Indeed, it is not uncommon that pregnant or lactating women with IBD require drug therapy, including monoclonal antibodies against Tumor Necrosis Factor-alpha (TNFα). However, these patients face challenges, because information on pregnancy and breastfeeding safety of these new medications is lacking due to exclusion of pregnant and breastfeeding women from drug development processes. Whereas the data necessary for fetal safety assessment is accumulating gradually, significant gaps in the research efforts and the understanding on excretion of TNFα inhibitors into milk remain. Experts generally consider it acceptable to use the TNFα inhibitors during breastfeeding, because the previous studies found relatively low levels of these drugs in milk. However, the existing data on milk levels of these drugs are highly inconsistent, probably because previous reports gave no consideration to potential interference from high levels of endogenous TNFα in milk. As a result, a comprehensive picture of TNFα inhibitors in breast milk remains obscure. Moreover, in a recent mouse study, transfer of TNFα-dependent chemokines through milk has been shown to play a role in shaping the postnatal programming of brain development, implying that altered disposition of endogenous TNFα and other chemokines in milk during anti-TNFα therapy has an impact on brain development of the offspring.

This is an observational cohort study with comparison group, which describes the first step to address the issue by uncovering the TNFα-dependent 'lactocrine' pathway and disposition of TNFα inhibitors in milk. The study will also investigate the pharmacokinetics of TNFα inhibitors in breast milk (as a sub-study), using the population pharmacokinetic (popPK) approach. ;

Related Conditions & MeSH terms

• Colitis
• Crohn Disease
• Crohn's Disease
• Healthy Controls
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Ulcerative Colitis

• NCT number: NCT03397108
• Study type: Observational
• Source: The Hospital for Sick Children
• Status: Active, not recruiting
• Start date: July 4, 2017
• Completion date: November 30, 2024