Crohn Disease, Inflammatory Bowel Diseases
Conditions
Keywords
Dietary intervention
Brief summary
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 billion 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.
Interventions
BEHAVIORALDietary education
Intervention: Low food additive diet. Control: Habitual food additive diet
Sponsors
The Leona M. and Harry B. Helmsley Charitable Trust
Guy's and St Thomas' NHS Foundation Trust
Institut Pasteur
King's College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged ≥16 years * CD diagnosis (defined by standard clinical, histological and radiological criteria) of at least 3 months * Mildly active disease as defined by: * Defined by physician assessment that no change in medication is required * Faecal calprotectin \>150 µg/g OR endoscopic evidence of active luminal disease OR radiological evidence of active luminal disease (by magnetic resonance enterography, or ultrasound) within the last 8 weeks. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Crohn's Disease Activity Index | Difference between baseline and week 8 | The proportion of patients achieving at least a 70-point reduction in the Crohn's Disease Activity Index from baseline to week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Faecal calprotectin | Baseline, 8 weeks and 26 weeks | The proportion of patients achieving at least a 50% reduction in faecal calprotectin concentration. |
| Serum C-reactive protein | Baseline, 8 weeks and 26 weeks | Absolute and change in CRP concentration and proportion of patients achieving a CRP concentration \<5 mg/L |
| Mucosal immune cell gene expression | Baseline and 8 weeks | RNA sequencing on GI immune cells isolated from rectal biopsies |
| Crohn's Disease Activity Index (CDAI) | Baseline, 8 weeks and 26 weeks | Absolute and change in CDAI score during the trial. |
| Stool Output | Baseline, 8 weeks and 26 weeks | Absolute and change in stool frequency and consistency |
| Perceived Crohn's disease control | Baseline, 8 weeks and 26 weeks | Absolute and change in score in IBD-control questionnaire |
| Health related quality of life | Baseline, 8 weeks and 26 weeks | Absolute and change in Inflammatory Bowel Disease questionnaire (IBDQ) score, and proportion of patients achieving clinical remission i.e., IBDQ score \>168 |
| Faecal microbiota composition | Baseline, 8 weeks and 26 weeks | Shotgun sequencing |
| Faecal microbial gene expression | Baseline, 8 weeks and 26 weeks (in a subset of participants) | Meta-transcriptomics |
| Mucosal microbiota composition | Baseline and 8 weeks (in a subset of participants) | 16S sequencing |
| Gastrointestinal permeability | Baseline and 8 weeks | Sugar probe solution urinary analysis to determine intestinal permeability |
| Dietary intake | Baseline, 8 weeks and 26 weeks | Micronutrient and macronutrient intake, food intake and dietary pattern |
| Dietary adherence | Baseline, 8 weeks and 26 weeks | Reduction in intake of food additives and consumption of study foods and snacks |
| Diet feasibility and acceptability | Baseline, 8 weeks and 26 weeks | Acceptability questionnaire, including food-related quality of life |
| Physical Activity | Baseline, 8 weeks and 26 weeks | International Physical Activity Questionnaire |
| Metabolomics | Baseline and 8 weeks | Metabolomics analyses through Liquid Chromatography - Mass Spectrometry using validated assays. |
| Biomarker study | Baseline and 8 weeks | Biomarker study through Nuclear Magnetic Resonance Spectroscopy |
| Genetics | Baseline | Whole genome single nucleotide polymorphism array genotyping |
Countries
United Kingdom
Outcome results
None listed