The ADDapt Diet in Reducing Crohn's Disease Inflammation

Study Overview
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Brief Summary
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Crohn's disease (CD) results in chronic intestinal inflammation, is of increasing incidence both in the developed and developing world and has a marked impact on patient quality of life. The prevalence of CD is 10.6 per 100,000 people in the UK and represents a significant annual financial burden of around €16.7 million in Europe. A wide range of nutrients and food components have been investigated for their role in the pathogenesis and course of CD. A common theme suggests that CD risk is associated with a Western diet, including high fat, high sugar and processed foods. However, intervention studies that exclude specific aspects of the diet such as sugar or that compare low and high fat diets have failed to show effectiveness in practice. Observational human and experimental animal studies suggest that certain food additives used extensively by the food industry play a role in the pathogenesis and natural history of CD. However, to date no evidence exists for the effectiveness of a diet low in these food additives in CD. Therefore, the aim of this study is to investigate the effects of a diet low in certain food additives compared to a normal UK diet on CD activity, health-related quality of life, gut bacteria, gut permeability, gut inflammation and dietary intake, in patients with mildly active, stable CD. We will recruit patients with mildly active CD and will randomise them to receive either the diet low in the food additives of interest, or the diet representative of a normal UK diet. Patients will follow their allocation diet for 8 weeks and will attend study visits at the start and end of the trial, at which points questionnaires will be completed and samples will be collected. Crohn's disease (CD) results in chronic intestinal inflammation, is of increasing incidence both in the developed and developing world and has a marked impact on patient quality of life. The prevalence of CD is 10.6 per 100,000 people in the UK and represents a significant annual financial burden of around €16.7 million in Europe. A wide range of nutrients and food components have been investigated for their role in the pathogenesis and course of CD. A common theme suggests that CD risk is associated with a Western diet, including high fat, high sugar and processed foods. However, intervention studies that exclude specific aspects of the diet such as sugar or that compare low and high fat diets have failed to show effectiveness in practice. Observational human and experimental animal studies suggest that certain food additives used extensively by the food industry play a role in the pathogenesis and natural history of CD. However, to date no evidence exists for the effectiveness of a diet low in these food additives in CD. Therefore, the aim of this study is to investigate the effects of a diet low in certain food additives compared to a normal UK diet on CD activity, health-related quality of life, gut bacteria, gut permeability, gut inflammation and dietary intake, in patients with mildly active, stable CD. We will recruit patients with mildly active CD and will randomise them to receive either the diet low in the food additives of interest, or the diet representative of a normal UK diet. Patients will follow the diet for 8 weeks and will attend study visits at the start and end of the trial, at which points questionnaires will be completed and samples will be collected.

Official Title
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The ADDapt Diet in Reducing Crohn's Disease Inflammation

Conditions
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Crohn Disease, Inflammatory Bowel Diseases

Intervention / Treatment
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* Behavioral: Dietary education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged ≥18 years CD diagnosis (defined by standard clinical, histological and radiological criteria) of at least 6 months Mildly active disease as defined by: Defined by physician assessment that no change in medication is required Faecal calprotectin >150 µg/g CDAI between 150-250 Current body weight of ≥50 kg Individuals able to give informed consent and willingness to participate Exclusion Criteria: Changes in dose to azathioprine, 6-mercaptopurine, methotrexate or anti-TNF-α agents or other biologics during the preceding 8 weeks, oral 5-ASA during the preceding four weeks. Currently receiving oral prednisolone/budesonide or discontinued within the last 4 weeks, unless they are on a stable dose of 10 mg/day or less prednisolone (3 mg or less budesonide) for at least 4 weeks with the intention to continue this long term. Used rectal 5-ASA or rectal steroids in the preceding 4 weeks Previous extensive bowel resection, defined as having had >2 intestinal resections, a sub-total colectomy or documented short bowel syndrome Poorly controlled bile acid malabsorption Current stoma Recent use of the following treatments: antibiotics, probiotics, prebiotic or fibre supplements in the preceding four weeks, NSAIDs during the preceding week Full bowel preparation for a diagnostic procedure in preceding 4 weeks Comorbidities including sepsis/fever, diabetes or coeliac disease, or other concomitant serious comorbidity e.g. significant psychiatric, hepatic, renal, endocrine, respiratory, neurological or cardiovascular disease Exclusive enteral nutrition in the past 8 weeks Assessed as at nutritional risk, as defined by any of the following: BMI ≤18.5 kg/m2 Previous or current eating disorder Currently receiving prescribed oral nutritional supplements Following a restrictive diet (e.g. multiple restrictions due to numerous self-reported allergies) as judged by the dietitian Reported pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low food additive diet<br>Dietary advice, given by a dietitian, will be discussed at trial baseline. | Behavioral: Dietary education<br>* Intervention: Low food additive diet. Control: Habitual food additive diet<br>|
| Placebo Comparator: Habitual food additive diet<br>Dietary advice, given by a dietitian, will be discussed at trial baseline. | Behavioral: Dietary education<br>* Intervention: Low food additive diet. Control: Habitual food additive diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Crohn's Disease Activity Index | The proportion of patients achieving at least a 70-point reduction in the Crohn's Disease Activity Index from baseline to week 8 | Difference between baseline and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Faecal calprotectin | The proportion of patients achieving at least a 50% reduction in faecal calprotectin concentration. | Baseline, 8 weeks and 26 weeks | 
| Faecal calprotectin | Absolute faecal calprotectin concentrations during the trial. | Baseline, 8 weeks and 26 weeks | 
| Faecal calprotectin | Proportion of patients achieving faecal calprotectin concentrations <150 µg/g. | Baseline, 8 weeks and 26 weeks | 
| Serum C-reactive protein | Absolute CRP concentration an proportion of patients achieving a CRP concentration <5 mg/L | Baseline, 8 weeks and 26 weeks | 
| Mucosal immune cell gene expression | RNA sequencing on GI immune cells isolated from rectal biopsies | Baseline and 8 weeks | 
| Crohn's Disease Activity Index (CDAI) | Change in CDAI score during the trial. | Baseline, 8 weeks and 26 weeks | 
| Crohn's Disease Activity Index (CDAI) | Proportion of patients achieving a CDAI score <150 points (clinical remission) by 8 weeks. | Baseline and 8 weeks | 
| Crohn's Disease Activity Index (CDAI) | Proportion of patients achieving ≥100-point reduction in CDAI score by 8 weeks. | Baseline and 8 weeks | 
| Perceived Crohn's disease control | Absolute score in IBD-control questionnaire | Baseline, 8 weeks and 26 weeks | 
| Health related quality of life | Inflammatory Bowel Disease questionnaire, IBDQ | Baseline, 8 weeks and 26 weeks | 
| Faecal microbiota composition | 16S sequencing | Baseline, 8 weeks and 26 weeks | 
| Faecal microbial gene expression | 16S RNA sequencing | Baseline, 8 weeks and 26 weeks (in a subset of participants) | 
| Mucosal microbiota composition | 16S sequencing | Baseline and 8 weeks (in a subset of participants) | 
| Gastrointestinal permeability | Sugar probe solution urinary analysis to determine intestinal permeability | Baseline and 8 weeks | 
| Dietary intake | Micronutrient and macronutrient intake | Baseline, 8 weeks and 26 weeks | 
| Dietary adherence | Reduction in intake of food additives | Baseline, 8 weeks and 26 weeks | 
| Diet feasibility and acceptability | Acceptability questionnaire, including food-related quality of life | Baseline, 8 weeks and 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary intervention