Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03397108 |
| Other study ID # |
1000056982 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 4, 2017 |
| Est. completion date |
November 30, 2024 |
Study information
| Verified date |
April 2024 |
| Source |
The Hospital for Sick Children |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
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.
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.
