Title: Dietary therapy to achieve and maintain mucosal healing in paediatric Crohn’s disease; a feasibility study
Funder: Department of Health and Social Care

Abstract: Background: Crohn s disease (CD) is an incurable, chronic, relapsing condition with 1 in 4 new diagnoses occurring in younger people. The disease is characterised by intestinal inflammation of unknown cause. Treatment aims to resolve intestinal inflammation and achieve healing of the intestinal mucosa as an optimal strategy to prevent disease flares and improve long-term outcomes. Exclusive enteral nutrition (EEN) is the recommended first-line treatment for paediatric CD (pCD). Over 85% of children/adolescents achieve clinical remission or improve during 6-8 weeks and EEN promotes mucosal healing. However, disease flares occur in most children within 12 months of re-starting a normal diet and significant intestinal inflammation persists in many children despite additional maintenance therapy with immune modulators and other drugs. Continuing some nutritional supplement alongside a normal diet may help to prevent flares but current nutritional supplements are not well accepted for longer-term use. Very little previous research has explored young people s/parents /carers perceptions and opinions regarding nutritional therapy for CD. Bovine colostrum (BC), the first milk of cows after parturition, contains several anti-inflammatory, anti-infective and growth factors that may reduce intestinal inflammation and promote mucosal healing in CD. Made-up as a flavoured milkshake, it may be acceptable for long-term use in children with CD. We plan to explore young people s/parents /carers perceptions and opinions regarding nutritional therapy and undertake a feasibility study of BC in pCD in preparation for a subsequent clinical trial. Research question: Is a daily supplement of BC acceptable for longer-term use in young people with CD and does it reduce intestinal inflammation and promote mucosal healing? Plan of investigation: We will engage children with CD and their parents/carers in the design and conduct of our study. Feasibility study: We will determine the recruitment rate, willingness to be randomized, adherence and adverse effects with a daily BC supplement, compliance with study procedures and participant retention over 3 months. We will generate preliminary data regarding the effect of BC in pCD to inform the effect size of a range of outcomes for a subsequent clinical trial. 50 young people with non-severe CD and stable disease will be recruited over 9 months and randomised 1:1 to receive a daily supplement of either BC or a matched comparator milk for 6 weeks in a double-blind trial. For the subsequent 6 weeks, all young people will be offered the daily BC supplement in an open study. Clinical (including weighted Paediatric Crohn s Disease Activity Index), laboratory and quality of life variables will be assessed at weeks 0, 5 and 11. Laboratory indices will include biomarkers of intestinal and systemic inflammation, mucosal function and integrity and growth factors. The effects of the BC supplement will be assessed by comparing the intervention and control groups at the end of week 5 and changes in variables before and after supplementation for 6 and 12 weeks. We consider that recruitment of 50 young people with CD is achievable and affordable and sufficient to generate the information required to design a subsequent trial. Qualitative research: We will invite 10 children from each arm of the study to participate in face-to-face or remote semi-structured interviews in weeks 1, 5 and 13. These will explore their perceptions and opinions regarding adherence to the dietary therapy, potential for long-term use, data and sample collection and outcomes that are important to them. Potential benefits to patients and the NHS: A dietary intervention acceptable for long-term use that was effective in promoting mucosal healing and prevented disease flares would likely improve long-term outcomes and quality of life. Maintenance dietary therapy may reduce drug use and the associated costs and adverse effects.

Lay abstract: Crohn s disease (CD) has become much more common in children and young people. The central problem is inflammation of the intestine causing abdominal pain, diarrhoea, weight loss and other complications. There is no cure; management aims to reduce the inflammation and then stop it from coming back. We know that many children who respond well to treatment (&ldquo;clinical remission&rdquo;) still have low-grade inflammation in the intestine and all are at risk of the disease flaring-up and progressing. New drugs have become available but are expensive, have side effects and despite their use many children struggle with on-going disease and require surgery. Remarkably, stopping usual foods and using only special feeds for up to 8 weeks without any drugs is highly effective and the recommended first-line treatment for CD in children. We need to further develop dietary management to see how it can be maintained long-term to reduce on-going inflammation and prevent flare-ups and disease progression. Bovine colostrum, the first milk produced by cows for their newborn calves, contains many factors that reduce inflammation and promote gut healing. It can be made-up as a flavoured milkshake, is affordable and safe even when given to sick patients and is being tested in premature babies and children and adults with leukaemia receiving chemotherapy. It is used by elite athletes to improve performance. In this initial study, we will assess children s/young people s and parents /carers interest in nutritional therapy. We will measure clinical and laboratory markers of persistent intestinal inflammation in children with CD receiving their usual maintenance therapy. We will test whether children with CD are able to take a daily supplement of bovine colostrum alongside a normal diet and whether this reduces intestinal inflammation. The findings will help us to develop further research in dietary therapy for children with inflammatory bowel disease.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL