A prospective, four-step interventional cohort treat-to-target study assessing the impact of a stepped diet program on faecal calprotectin and CRP in Crohn’s disease.

Treat-to-target, step-up program of up to 4 diets, which increase in prescriptiveness, as sole or adjunctive therapy for Crohn’s disease. Step 1: Wholefood, Mediterranean-style diet. Step 2: Phase 2 of the Crohn’s Disease Exclusion Diet (CDED); Step 3: Phase 1 of the CDED; Step 4: A formulated, liquid only diet, known as Exclusive Enteral Nutrition (EEN). All interventions will be administered by dietitians. Dietitians will provide education materials and a meal plan. Liquid nutrition formula will be provided on EEN, but food will not be provided. Patients will have in-person visits with a dietitian at Baseline, end of Week 1, End of Week 6, End of Week 12, 6 months will follow up (completion of questionnaires) at 12 months. 24 months, and 2-yearly thereafter for up to 10 years or as long as clinically relevant. The assessment criteria for step up to the next phase diet at each 6 weekly visit is FAILURE to meet the following definition of response (primary endpoint criteria): Biochemical response (faecal calprotectin decrease of more than or equal to 50% from baseline or to less than or equal to 100ug/L OR CRP decrease by more than or equal to 50% or reaching normal level). We will assess biomarkers to determine participant response after 6 weeks on the diet, to determine if the participant will move to the next diet phase due to non-response. Alternatively, a clinical response has occurred, the patient will be transitioned to the wholefood diet for maintenance therapy, which does not exclude any food groups, and is in concordant with the Australian Guide to Healthy Eating. Dietary intensification will be immediate (no washout-our ot run-in period) That is, the maximum time on any one of the four therapeutic will be 12 weeks, and the maximum total time of active intervention will be 24 weeks. All patients will have at least 12 weeks of active intervention. Patients will follow allocated diet for entire time they are allocated to that diet arm (all meals and snacks). Step 1: Additive Free, Wholefood (Mediterranean Style) Diet This diet was designed by the researchers. The main focus of this diet is the exclusion of added chemicals and additives in food. Most processed foods contain chemicals to make them look better, last longer, or taste different. Many of these chemicals, however, are known to be pro-inflammatory. Foods can be classified in tiers of processing by the NOVA classification. Natural (unprocessed) foods are allowed. Natural foods include fresh, chilled and frozen fruits and vegetables; legumes such as beans and lentils; nuts and seeds; fresh meat, poultry and fish; eggs; milk and some yoghurts. Grains, such as oats, rice, polenta and quinoa and flours/flakes/pastas made from grains are also considered natural as although they have undergone some mechanical processing, they generally contain no chemical additives. Processed food ingredients generally do not contain added chemicals and can be kept in the diet. These are usually used to cook fresh foods and are rarely consumed alone. Examples include olive oil and other vegetable oils (sunflower, canola, etc.), salt, sugar, honey and vinegar. Processed foods with these minor additions (i.e., salt, sugar oil) but no chemicals can also be kept in the diet. Examples include some corn chips, potato crisps, nut butters, and certain crackers/breads/breakfast cereals. Processed foods often contain additives to preserve their original properties or prevent spoilage. Examples include tinned vegetables and fruits, cured meats, cheese and bread. The labels of these foods need to be checked before deciding if they are acceptable to consume on this diet. Ultra-processed foods (NOVA group 4) have long lists of unrecognisable ingredients and added chemicals with minimal intact, natural foods. Examples include fizzy drinks, packaged snacks, ice-cream, chocolate, packaged breads, margarines, biscuits, pastries, cakes, and chicken and fish ‘nuggets’ and ‘sticks’, sausages and burgers. These foods should be completely avoided. In addition to recommending avoidance of dietary additives, this diet recommends reduced consumption of red meat (1/week), with a focus on chicken, eggs and legumes as protein sources; reduced consumption of wheat-containing products (1/day), with a focus on consuming a diverse range of wholegrains; low moderate alcohol consumption; use of monounsaturated fatty acids (e.g. olive oil) in cooking; and inclusion of unprocessed fruit, vegetables and dairy daily. The Additive Free, Wholefood (Mediterranean Style) Diet will be utilised as the first entry point therapeutic diet option and the maintenance dietary therapy. Step 2 (Phase 1 of CDED) and Step 3 (Phase 2 of CDED) The Crohn’s Disease Exclusion Diet (CDED) is a 3-phase diet. The diet mainly focuses on: • Avoidance of added chemicals • Inclusion of high-quality, low-fat protein (mostly chicken and eggs) • Inclusion of resistant starch and specific fibres (apples, bananas, potatoes) • Use of liquid supplements to help meet energy and nutrient needs In addition, the diet limits dairy, wheat, oats, quinoa, red meat, and fish. These must be completely avoided in the first six weeks and consumed in restricted amounts long term. Certain fruits and vegetables are also restricted in the initial phase of the diet. The diet becomes less restrictive as you move through the phases. In brief: Phase 1: Follow for 6 weeks, every day consume 50% of your daily energy as liquid supplements, and eat eggs, chicken, potatoes, apple, and bananas daily. Plus, eat unlimited rice, rice noodles and limited amounts of some fruit and vegetables Phase 2: Follow for 6 weeks, every day consume 25% of your daily energy as liquid supplements and eat eggs, chicken, potatoes, apple, bananas. Plus, eat unlimited rice, rice noodles, start introducing some additional grains, fruits, and vegetables not allowed during phase 1. Exclusive Enteral Nutrition EEN is a complete liquid diet, in which patients only consume commercial oral nutrition supplements (nil other foods or beverages permitted). The amount of EEN recommended to participants will be based on individual energy requirements, calculated using the Scofield equation. Supplements will be provided to patients through the Home Enteral Nutrition (HEN) scheme. The participants will be commenced on the chosen therapeutic diet for an initial 6 week period, after which they will be assessed for response. If the response criteria are met, they will complete a further 6 weeks on the same therapeutic diet they were previously following (for a total of 12 weeks on the therapeutic diet), and then transition to the maintenance phase - the Step 1: Additive free, Wholefood ‘Mediterranean-style diet’. If the response criteria are NOT met at 6 weeks, they will be escalated to the next more intensive diet, and then reassessed for response at 6 weeks. If the response criteria are then met after the next 6 week period (on the second intensified diet), they will complete a further 6 weeks on the therapeutic diet (for a total of 12 weeks on the therapeutic diet), and then transition to the maintenance phase - the Step 1: Additive free, Wholefood ‘Mediterranean-style diet’. Adherence will be monitored using 24-hr diet recalls, a modified medication adherence scale, and the CDED adherence scale.