Crohn's DiseaseNCT03397108
Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease
An observational study of Crohn's Disease and Ulcerative Colitis, run by The Hospital for Sick Children at 2 sites in Canada.
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. 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Crohn's Disease, Ulcerative Colitis, Healthy Controls
- What is being tested?
- The IBD group was divided into 2 subgroups: with or without anti-TNF antibody use
- How many people
- 79 participants
- Where
- 2 sitesCanada
- Study dates
- 31 Aug 2017to 5 Nov 2024
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study participants are required to live in the Greater Toronto Area. The IBD group will be selected from IBD clinics, while the healthy controls will be selected from the community samples who volunteer to participate.
Who may be able to join
- Breastfeeding women with IBD or healthy breastfeeding women in the first 4-month postpartum period
Who cannot join
- unable to communicate in English
- Present illness of chronic inflammatory conditions (except IBD)
- Mastitis
- Present acute or chronic infection
- use of a different anti-Tumor Necrosis Factor (TNF) drug within the last 2 months
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
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.
Read more
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.
Read the detailed 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 (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:
Because there was no information at the outset of the study on cytokine profiles in milk of women with inflammatory conditions including IBD, a formal sample size could not be estimated. Although a provisional target was set, the study was designed to continue for the planned study duration as no stopping rule had been defined. Also, our original protocol included a population pharmacokinetic study of TNFmAb in milk. However, due to the pandemic and difficulty in developing the assay method, we were not able to start this part of the project.
- Conditions
- Crohn's Disease, Ulcerative Colitis, Healthy Controls
- Being tested
- The IBD group was divided into 2 subgroups: with or without anti-TNF antibody use
- Keywords
- Inflammatory Bowel Disease, Crohn disease, Colitis, TNF, Breast milk, monoclonal antibody
- Medical subject headings
- Crohn Disease, Colitis, Ulcerative, Inflammatory Bowel Diseases, Colitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The IBD group was divided into 2 subgroups: with or without anti-TNF antibody useOther
This observational study enrolled women with IBD, and some of them were receiving a treatment with anti-TNF monoclonal antibody, which was prescribed by their responsible prescribers at a standard dose and dosing interval.
| Study group | Role | What they receive |
|---|---|---|
| Women with IBD | This group is composed of breastfeeding women aged over 18 years and in their first 4-month postpartum period, who are diagnosed with Crohn's disease or Ulcerative Colitis. Some of them were receiving anti-TNF monoclonal antibody prescribed by their prescribers (outside this observational study) at a standard dose and interval. Receives: Other: The IBD group was divided into 2 subgroups: with or without anti-TNF antibody use | |
| Healthy breastfeeding women | This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: Two points at early-lactation (median 5-6 postpartum weeks) and mid-lactation (median 13-14 postpartum weeks)
Secondary outcomes (1)
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
We used Bayley Scales of Infant and Toddler development- Third Version (Bayley-III): which is used widely to measure child's cognitive and language development. In this scale, for both cognitive and language scores, minimum standard score is 45 and maximum standard score is 155: Higher standard scores indicates stronger/better performance.
Children of the participating mothers were tested at the age of 12 months and 18 months. The language assessment is also used for comprehensiveness, but this has been added after the study was started. The test is performed as a single-blinded assessment in a controlled environment at the Hospital for Sick Children by a trained psychometrist supervised by a psychologist.
Measured: At the infant age of 12 months and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2018
- Study start31 Aug 2017
- Primary completion30 Nov 2022
- Study completion5 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- MOUNT SINAI HOSPITAL, Crohn's and Colitis Foundation
- Responsible party
- Principal investigator, Shinya Ito, The Hospital for Sick Children
- Investigators
- Shinya Ito, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03397108
- Sponsor's protocol ID
- 1000056982
- Status last verified
- Feb 2025
- First submitted
- 19 Dec 2017
- Last updated
- 4 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participant-level data collected during the study will be available for research purposes in a form of de-identified individual data upon reasonable request. Other research documents such as study protocol may be also available. This data sharing activity is contingent upon approval from the institutional research ethics board of the Hospital for Sick Children. An interested party may submit a proposal to the study team up to 36 months following article publication, describing the purpose and methods of data use. Data requestors may need to sign a data transfer agreement.
Publications
Maron JL. The importance of investigating the effects of drug therapy on maternal breast milk composition. Pediatr Res. 2025 May;97(6):1765-1766. doi: 10.1038/s41390-024-03785-1. Epub 2024 Dec 13. No abstract available.
PubMed 39672826Sepiashvili L, Brydon A, Koroshegyi C, Gold A, Dalvi P, Ghayoori S, Rahman M, Huang V, Maxwell C, Nguyen GC, Ito S. Reduction of tumor necrosis factor (TNF) in milk of women receiving anti-TNF antibody. Pediatr Res. 2025 May;97(6):1935-1942. doi: 10.1038/s41390-024-03672-9. Epub 2024 Nov 1.
PubMed 39487320
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease
- ClinicalTrials.gov ID
- NCT03397108
- Acronym / sponsor ID
- 1000056982
- Conditions
- Crohn's Disease, Ulcerative Colitis, Healthy Controls
- Keywords
- Inflammatory Bowel Disease, Crohn disease, Colitis, TNF, Breast milk, monoclonal antibody
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- MOUNT SINAI HOSPITAL, Crohn's and Colitis Foundation
- Study start
- 31 Aug 2017 (actual)
- Primary completion
- 30 Nov 2022 (actual)
- Study completion
- 5 Nov 2024 (actual)
- First posted
- 11 Jan 2018 (actual)
- Results
- Posted 4 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 (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:
Because there was no information at the outset of the study on cytokine profiles in milk of women with inflammatory conditions including IBD, a formal sample size could not be estimated. Although a provisional target was set, the study was designed to continue for the planned study duration as no stopping rule had been defined. Also, our original protocol included a population pharmacokinetic study of TNFmAb in milk. However, due to the pandemic and difficulty in developing the assay method, we were not able to start this part of the project.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Women with IBD | – | Other: The IBD group was divided into 2 subgroups: with or without anti-TNF antibody useThis group is composed of breastfeeding women aged over 18 years and in their first 4-month postpartum period, who are diagnosed with Crohn's disease or Ulcerative Colitis. Some of them were receiving anti-TNF monoclonal antibody prescribed by their prescribers (outside this observational study) at a standard dose and interval. |
| Healthy breastfeeding women | – | –This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study participants are required to live in the Greater Toronto Area. The IBD group will be selected from IBD clinics, while the healthy controls will be selected from the community samples who volunteer to participate.
Key inclusion criteria (1 listed)
- Breastfeeding women with IBD or healthy breastfeeding women in the first 4-month postpartum period
Key exclusion criteria (5 listed)
- unable to communicate in English
- Present illness of chronic inflammatory conditions (except IBD)
- Mastitis
- Present acute or chronic infection
- use of a different anti-Tumor Necrosis Factor (TNF) drug within the last 2 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The IBD group was divided into 2 subgroups: with or without anti-TNF antibody useThis observational study enrolled women with IBD, and some of them were receiving a treatment with anti-TNF monoclonal antibody, which was prescribed by their responsible prescribers at a standard dose and dosing interval. | Other | Women with IBD |
Primary outcome
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
Time frame: 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.
1 secondary outcome
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
Time frame: At the infant age of 12 months and 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 39672826Maron JL. The importance of investigating the effects of drug therapy on maternal breast milk composition. Pediatr Res. 2025 May;97(6):1765-1766. doi: 10.1038/s41390-024-03785-1. Epub 2024 Dec 13. No abstract available.
- Results publication: PubMed 39487320Sepiashvili L, Brydon A, Koroshegyi C, Gold A, Dalvi P, Ghayoori S, Rahman M, Huang V, Maxwell C, Nguyen GC, Ito S. Reduction of tumor necrosis factor (TNF) in milk of women receiving anti-TNF antibody. Pediatr Res. 2025 May;97(6):1935-1942. doi: 10.1038/s41390-024-03672-9. Epub 2024 Nov 1.
- Individual participant dataSharing planned: Yes. Participant-level data collected during the study will be available for research purposes in a form of de-identified individual data upon reasonable request. Other research documents such as study protocol may be also available. This data sharing activity is contingent upon approval from the institutional research ethics board of the Hospital for Sick Children. An interested party may submit a proposal to the study team up to 36 months following article publication, describing the purpose and methods of data use. Data requestors may need to sign a data transfer agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shinya Ito, MD principal investigator
The Hospital for Sick Children
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Crohn's Disease and Ulcerative Colitis, run by The Hospital for Sick Children at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Two points at early-lactation (median 5-6 postpartum weeks) and mid-lactation (median 13-14 postpartum weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03397108, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2025.