Combinatietherapie van medicijnen en een dieet om remissie te bereiken bij kinderen en jongeren met milde tot matige Colitis Ulcerosa.

Recent evidence suggests that environmental factors and diet in particular may play an important role in IBD pathogenesis, with the strongest evidence to date for Crohn’s disease. Understanding of these processes facilitated development of effective dietary therapies for patients with CD. To date, there is no proven dietary intervention that may help patients with ulcerative colitis (UC). On the microbiota side, UC is characterized by decreased production of short chain fatty acids (SCFA) and increased Proteobacteria and sulfide-reducing bacteria ( SRBs). From the host’s perspective, a decrease in goblet cells and mucin production coupled with a permeable mucous layer is demonstrated in UC. Each of these observations can be linked to factors found in Western diet that may promote and accelerate intestinal inflammation. As an example, soy and casein have been shown to exacerbated dextran-sodium sulfate (DSS) colitis in mice and dairy fat was shown to induce colitis in a rodent model as well. The PIBD research center at WMC has developed a diet (UC Diet, or UCD) based on restriction and addition of dietary components that may affect the host mucous layer or microbiome, based on these observations. This diet is rich in fruits and vegetables but reduces exposure to certain animal-based sources of protein and fat while favoring other animal sources of protein and healthy oils. In two ongoing pilot trials to evaluate efficacy in patients with mild to moderate UC who have failed induction on 5ASA therapy or relapsed on 5ASA ( 5ASA failures), this led to a clinical response in 17/19 (88%) and a steroid-free clinical remission in 9/19 (47%) of treatment courses in children and 3/6 (50%) in adults (2 with complete mucosal or near complete healing after 8 weeks). These results imply that diet could play a more important role in induction of remission than currently appreciated.

Objective of the study:
In the current study we will attempt to evaluate if the diet, termed the UC Diet (UCD), can improve outcomes when administered with a 5ASA regimen to pediatric patients with mild-moderate UC, through a single blinded multinational RCT.

Study design:
This will be a 12 week, single blinded RCT in children and adolescents with mild to moderate UC comparing 5ASA (recommended dosing 60-75 mg/kg/day; minimum 2.5 maximum 4 grams/day) with fiber restriction for 6 weeks followed by free diet (Group 1) to 5ASA with UCD for 6 weeks, followed by the step down UCD for the next 6 weeks.

Study population:
The study population will comprise 62 UC patients, aged 10-19, weighing at least 30 kg, with mild to moderate active disease defined by the Pediatric UC Activity Index (10 ≤PUCAI≤45), at diagnosis or despite stable maintenance therapy with 5ASA ≤ 2grams or thiopurines for at least 8 weeks.

Intervention (if applicable):
Current clinical practice is to reduce exposure (now withhold fiber) to fiber during active bleeding and diarrhea and to gradually increase access to grains fruit and vegetables once patients improve. This practice has no evidence behind it and was based on common sense. We will compare two dietary strategies, insoluble fiber reduction via current practice in each site to the UC Diet. The UC diet will restrict certain sources of animal protein, animal fat, and emulsifiers and food additives during the 12week period, while allowing access to fruit, vegetables, and certain grains. It is not a vegan or vegetarian diet as it contains portions of chicken and eggs. It will be structured with mandatory foods, foods that are restricted to certain days or certain quantities, and other foods that are unlimited, to provide better food related quality of life. Both groups will receive a calcium supplement and vitamin D supplement for 6 weeks. Dietitians will assess dietary intake of calories and food groups at week 0 and 6 and will assess compliance by local analysis of food diaries. Intolerance to diet will be defined as patients stopping the diet because of difficulty with the diet ( not because of inadequate response).

We hypothesize that the UC Diet (UCD) can improve induction of remission rates when administered with a 5ASA regimen to pediatric patients with mild-moderate UC vs. 5ASA regimen alone.

0,2,3,6,12 weeks

UC Diet