Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 79
- 试验地点
- 2
- 主要终点
- Levels of TNF (Tumor Necrosis Factor Alpha) and TNF-dependent Chemokines (MCP1, MIP-1beta and IP10) in Breast Milk of Women With IBD and Healthy Controls by Multiplex Assay
研究概览
简要总结
Breastfeeding is beneficial to both mother and baby. However, many breastfeeding women are affected by long-term health conditions and need to take medications.
Inflammatory Bowel Disease (IBD) 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 TNF). 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 observational study is 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 TNF and some other cytokines are higher in breast milk of women with IBD, and the biologics can normalize these high levels.
Note: Due to the pandemic, the study now consists of reduced number of 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.
详细描述
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 (TNF).
TNF and TNF-dependent chemokines are normally expressed in milk. Importantly, experimental data indicate enhanced brain growth and cognitive development in the mouse offspring given milk deficient in TNF and TNF-dependent chemokines. Patients with IBD are often treated with monoclonal antibodies against TNF (TNFmAb). Although TNFmAb is used during breastfeeding due to their minimal milk excretion, whether it affects endogenous TNF/chemokines in human milk is not known.
Our hypotheses are: 1) Women with IBD have higher TNF (and TNF-dependent chemokines) in milk than non-IBD control women, because of the inflammatory condition; and 2) Women with IBD receiving TNFmAb have lower TNF (and TNF-dependent chemokines) in milk than those with IBD who are not treated with TNFmAb.
We conduct an observational study of breastfeeding women with or without IBD. Some of these women with IBD are likely to be receiving TNFmAb. We measure milk concentrations of TNF and TNF-dependent chemokines in early (5-6 weeks postpartum) and mid-lactation period (13-14 weeks postpartum). Also, as an exploratory analysis, we assess their infant's cognitive and language development at 12 month and 18 months using Bayley-III tool.
Note:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Breastfeeding women with IBD or healthy breastfeeding women in the first 4-month postpartum period
排除标准
- •unable to communicate in English
- •Present illness of chronic inflammatory conditions (except IBD)
- •Present acute or chronic infection
- •use of a different anti-Tumor Necrosis Factor (TNF) drug within the last 2 months
结局指标
主要结局
Levels of TNF (Tumor Necrosis Factor Alpha) and TNF-dependent Chemokines (MCP1, MIP-1beta and IP10) in Breast Milk of Women With IBD and Healthy Controls by Multiplex Assay
时间窗: Two points at early-lactation (median 5-6 postpartum weeks) and mid-lactation (median 13-14 postpartum weeks)
This observational study collected milk samples during the defined study periods: early-lactation and mid-lactation. To capture a temporal profiles of Tumour Necrosis Factor (TNF) and TNF-dependent chemokine levels, we analyzed these 2 sampling periods separately, instead of pooling them per sampling period. Multiplex assay was used to measure TNF and TNF-dependent downstream chemokines including MCP-1 (CCL2), MIP-1beta (CCL4) and IP10 (CXCL10) in breast milk of two groups of participants (women with IBD and healthy controls) at two sampling periods (early- and mid-lactation). Our original plan included MCP-3 (CCL7) as well, but an average quantification rate for this chemokine was only 33%, and therefore we excluded MCP-3 from our analyses.
次要结局
- Scores on Cognitive Subset of Bayley Scales of Infant and Toddler Development- Third Version (Bayley-III) in Infants of Healthy Controls and Women With IBD(At the infant age of 12 months and 18 months)
研究者
Shinya Ito
Principal Investigator, Head of Clinical Pharmacology & Toxicology
The Hospital for Sick Children