Is cows’ "first milk" an acceptable and effective way of improving gut health and nutrition in children with Crohn’s disease?
| ISRCTN | ISRCTN78570360 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78570360 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | 246070; CPMS: 39688 |
| Sponsor | Alder Hey Children's NHS Foundation Trust |
| Funder | Research for Patient Benefit Programme |
- Submission date
- 01/07/2019
- Registration date
- 08/07/2019
- Last edited
- 02/12/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
Crohn’s disease (CD) is an incurable, long-lasting, inflammatory bowel disease that causes pain, diarrhoea and reduced growth. CD can result in poor quality of life, illness and high treatment costs. The first recommended treatment in young people is exclusive enteral nutrition (EEN). This is when a special milk feed is given as the sole source of food for 6-8 weeks. Over 85% of children with active CD stop experiencing symptoms or show improvement of symptoms during EEN. The problem is that disease flares often occur after the young person’s usual diet is re-introduced. Continuing some of a special milk every day may help to maintain gut health and nutrition and reduce the risk of disease flares. However, many young people dislike the special milks and are not able to take them long-term. There is a need for dietary therapy that is effective but also acceptable for longer-term use.
This study aims to investigate whether “First Milk” taken daily alongside a young person’s usual diet is acceptable for long-term use and whether it may improve gut health and nutrition. First Milk or pre-milk is produced by cows after giving birth and is also called bovine colostrum. It contains high levels of naturally occurring substances that may reduce inflammation and help to repair and reduce the leakiness of the intestinal lining in CD. First Milk also improves defenses against infection. Only a small amount of First Milk may be needed every day to improve gut health and nutrition in CD. First Milk is tasteless and many different flavourings can be used to make a milkshake which may improve acceptability for long-term use.
Who can participate?
50 young people aged 8-18 years with stable mild or moderate CD. Young people who are allergic to, or intolerant to, cow’s milk and those already taking a dietary supplement will not be able to participate.
What does the study involve?
Participants will be allocated randomly to receive either First Milk or a normal cow's milk powder every day for 6 weeks and will not know which milk they are receiving. This is the “blinded” phase of the study. From weeks 7 to 12, all participants will receive daily First Milk in the “open” phase. How young people manage with the supplement will be recorded in a daily diary. They can also provide blood and stool samples and do sugar absorption tests that will require them to provide urine samples to monitor gut leakiness. These samples will be collected at the beginning of the study and at weeks 6 and 12.
20 young people and their families who are taking part in the study will be interviewed to assess their perceptions and opinions of dietary therapy, First Milk and the research methods.
All of the information collected will help to assess whether or not First Milk might have a useful role in managing CD. If so, the information from this initial study will allow a larger study to be designed to assess the effects of First Milk on important clinical outcomes such as the prevention of disease flares.
What are the possible benefits and risks of participating?
All of the young people in the study will take the First Milk daily for either 6 or 12 weeks. This may improve their gut health and nutritional status. It is unlikely that taking the comparison milk would result in any benefits. First Milk has been taken by over 2000 people in research studies for many different illnesses. No serious side effects have been reported. Some people have reported feeling nauseous, flatulence, diarrhoea, skin rash, and unspecified tummy discomfort; however, these possible side effects have been mild. Therefore, we do not anticipate that either of the milks will cause any harm in young people who are not allergic to, or intolerant to, cow’s milk. The clinical and laboratory measurements being done in the study are for research and will not help the treatment of individual young people. Taking part in the study will require providing information and samples, but these are not considered to pose any risk.
Where is the study run from?
Alder Hey Children’s Hospital (UK)
When is the study starting and how long is it expected to run for?
April 2018 to July 2021 (updated 11/06/2021, previously: June 2021; updated 08/03/2021, previously: March 2021)
Who is funding the study?
The NIHR Research for Patient Benefit Scheme (UK)
Who is the main contact?
Prof. Stephen Allen
Stephen.allen@lstmed.ac.uk
Contact information
Scientific
Clinical Sciences Department
Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
L3 5QA
United Kingdom
 ORCID ID |
0000-0001-6675-249X |
|---|---|
| Phone | +44 (0)151 705 3752 |
| stephen.allen@lstmed.ac.uk |
Scientific
Gastroenterology Department 2A
Alder Hey Children’s NHS Foundation Trust
Eaton Road
Liverpool
L12 2AP
United Kingdom
| Phone | +44 (0)1512284811 ext. 4041 |
|---|---|
| Janet.clark@alderhey.nhs.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Prospective qualitative trial and randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Dietary therapy with bovine colostrum to improve nutrition and gut health in paediatric Crohn’s disease; a feasibility study |
| Study objectives | 1. First Milk is acceptable to children and their parents/carers for long-term use (3 months) and free of significant adverse effects 2. Children/young people with Crohn's disease (CD) and their parents/carers are interested in participating in research of dietary therapy as a possible safe, acceptable and long-term means of controlling intestinal disease 3. It is possible to perform additional sample collection and procedures alongside usual clinical care to enable assessment of novel dietary interventions 4. First Milk improves biomarkers of nutrition and gut health in paediatric CD |
| Ethics approval(s) | Approved 06/11/2018, North West - Liverpool East Research Ethics Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ; nrescommittee.northwest-liverpooleast@nhs.net), ref: 18/NW/0637 |
| Health condition(s) or problem(s) studied | Crohn's disease in children |
| Intervention | Young people will be randomised 1:1 to the two study arms (weeks 1-6) using a computer-generated random allocation sequence with blocks of varied size generated and held by the CTU at LSTM. A Research Nurse will allocate children at baseline to the next unique research number in the allocation sequence. Plain bags of the appropriate milk powder, identified only by the unique research number, will be prepared in advance according to the random sequence. The Research Nurse will provide the young person/family with the appropriate milk powder. First Milk study arm: 20 g/day of First Milk tasteless powder. Comparator study arm: 20 g/day of a mix of skimmed milk powder (70%) and milk protein concentrate (30%) to make a matched comparator with equivalent protein and lactose content. Both milks can be made up with about 150 ml semi-skimmed milk, full cream milk, water or other fluids. In both study arms, the dose could be reduced to 10 g/day if a larger volume is not tolerated and a range of flavourings can be added according to personal preference to make a palatable milkshake. Either First Milk or the comparator milk are given for the first 6 weeks of the study (blinded phase). For weeks 7-12, all young people will receive First Milk (open phase). |
| Intervention type | Supplement |
| Primary outcome measure(s) |
Compliance with dietary supplement recorded in a daily diary collected during weeks 2, 6 and 12 and during weekly phone calls |
| Key secondary outcome measure(s) |
1. Young people’s and parent's/carers’ perceptions and views regarding dietary therapy and on participating in research on dietary therapy assessed using interviews conducted at the end of the first week, end of week 6 and after completion of the intervention by week 13-14 |
| Completion date | 26/07/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 8 Years |
| Sex | All |
| Target sample size at registration | 50 |
| Total final enrolment | 23 |
| Key inclusion criteria | 1. Aged 8 years and above 2. CD in clinical remission or mild/moderate disease severity (weighted pCD Activity Index [wPCDAI] ≤57.5) 3. Stable clinical condition defined as either receiving no treatment or maintenance therapy that has been unchanged for at least the last 2 months with no intention to change therapy at the time of recruitment 4. Willing for clinical information to be used for the purposes of the trial 5. Willing to partake in the study procedures 6. Able to complete the daily diary in English |
| Key exclusion criteria | 1. Severe CD (wPCDAI >57.5) 2. Intolerance of dairy products 3. Receiving dietary therapy for the management of Crohn’s disease (e.g. Modulen IBD) 4. Already taking BC regularly 5. Established diagnosis of a significant gut disorder other than CD (e.g. short bowel syndrome) 6. Failure to obtain informed consent from the patient and/or parent/guardian |
| Date of first enrolment | 18/02/2019 |
| Date of final enrolment | 08/04/2021 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Liverpool
L14 5AB
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Stored in publicly available repository, Available on request |
| IPD sharing plan | Informed consent has been secured for the anonymised demographic, clinical and laboratory datasets generated during the current study to be publicly accessible through a central data management system at the Liverpool School of Tropical Medicine or available on request from Prof Stephen Allen; Stephen.allen@lstmed.ac.uk). Data will be available for a minimum of 5 years after publication of the study results. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 01/11/2022 | 02/12/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version v0.7 | 15/10/2018 | 05/07/2021 | No | No |
Additional files
- ISRCTN78570360_PROTOCOL_v0.7_15Oct18.pdf
- Uploaded 05/07/2021
Editorial Notes
02/12/2022: Publication reference added.
05/08/2022: The following changes have been made:
1. The intention to publish date was changed from 30/09/2022 to 30/12/2022.
2. The individual participant data (IPD) sharing statement "Stored in publicly available repository" has been added.
28/03/2022: The intention to publish date was changed from 30/03/2022 to 30/09/2022.
31/12/2021: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2021 to 08/04/2021.
2. The overall trial end date has been changed from 15/07/2021 to 26/07/2021.
3. The intention to publish date has been changed from 31/12/2021 to 30/03/2022.
12/07/2021: The overall trial end date has been changed from 28/07/2021 to 15/07/2021.
05/07/2021: Uploaded protocol version 0.7, 15 October 2018 (not peer reviewed).
11/06/2021: The following changes have been made:
1. The overall trial end date has been changed from 30/06/2021 to 28/07/2021 and the plain English summary has been updated to reflect this change.
2. The total final enrolment number has been added.
08/03/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/06/2020 to 31/03/2021.
2. The overall end date was changed from 31/03/2021 to 30/06/2021.
3. The intention to publish date was changed from 31/03/2021 to 31/12/2021.
4. The plain English summary was updated to reflect these changes.
5. The recruitment resumed.
15/04/2020: Due to current public health guidance, recruitment for this study has been paused.
06/11/2019: Contact details updated.
29/10/2019: The following changes were made to the trial record:
1. Contact details updated.
2. The recruitment end date was changed from 30/06/2019 to 30/06/2020.
3. The overall trial end date was changed from 30/09/2019 to 31/03/2021.
29/07/2019: Internal review.
15/07/2019: Internal review.
03/07/2019: Trial's existence confirmed by North West - Liverpool East Research Ethics Committee.
