The ADDapt Diet in Reducing Crohn's Disease Inflammation
Study Details
Study Description
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 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Low food additive diet Dietary advice, given by a dietitian, will be discussed at trial baseline. |
Behavioral: Dietary education
Intervention: Low food additive diet. Control: Habitual food additive diet
|
| Placebo Comparator: Habitual food additive diet Dietary advice, given by a dietitian, will be discussed at trial baseline. |
Behavioral: Dietary education
Intervention: Low food additive diet. Control: Habitual food additive diet
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Faecal calprotectin [Baseline, 8 weeks and 26 weeks]
The proportion of patients achieving at least a 50% reduction in faecal calprotectin concentration.
- Faecal calprotectin [Baseline, 8 weeks and 26 weeks]
Absolute faecal calprotectin concentrations during the trial.
- Faecal calprotectin [Baseline, 8 weeks and 26 weeks]
Proportion of patients achieving faecal calprotectin concentrations <150 µg/g.
- Serum C-reactive protein [Baseline, 8 weeks and 26 weeks]
Absolute CRP concentration an 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]
Change in CDAI score during the trial.
- Crohn's Disease Activity Index (CDAI) [Baseline and 8 weeks]
Proportion of patients achieving a CDAI score <150 points (clinical remission) by 8 weeks.
- Crohn's Disease Activity Index (CDAI) [Baseline and 8 weeks]
Proportion of patients achieving ≥100-point reduction in CDAI score by 8 weeks.
- Perceived Crohn's disease control [Baseline, 8 weeks and 26 weeks]
Absolute score in IBD-control questionnaire
- Health related quality of life [Baseline, 8 weeks and 26 weeks]
Inflammatory Bowel Disease questionnaire, IBDQ
- Faecal microbiota composition [Baseline, 8 weeks and 26 weeks]
16S sequencing
- Faecal microbial gene expression [Baseline, 8 weeks and 26 weeks (in a subset of participants)]
16S RNA sequencing
- 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
- Dietary adherence [Baseline, 8 weeks and 26 weeks]
Reduction in intake of food additives
- Diet feasibility and acceptability [Baseline, 8 weeks and 26 weeks]
Acceptability questionnaire, including food-related quality of life
Eligibility Criteria
Criteria
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:
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Defined by physician assessment that no change in medication is required
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Faecal calprotectin >150 µg/g
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CDAI between 150-250
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Current body weight of ≥50 kg
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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.
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Used rectal 5-ASA or rectal steroids in the preceding 4 weeks
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Previous extensive bowel resection, defined as having had >2 intestinal resections, a sub-total colectomy or documented short bowel syndrome
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Poorly controlled bile acid malabsorption
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Current stoma
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Recent use of the following treatments: antibiotics, probiotics, prebiotic or fibre supplements in the preceding four weeks, NSAIDs during the preceding week
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Full bowel preparation for a diagnostic procedure in preceding 4 weeks
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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
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Exclusive enteral nutrition in the past 8 weeks
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Assessed as at nutritional risk, as defined by any of the following:
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BMI ≤18.5 kg/m2
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Previous or current eating disorder
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Currently receiving prescribed oral nutritional supplements
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Following a restrictive diet (e.g. multiple restrictions due to numerous self-reported allergies) as judged by the dietitian
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Reported pregnancy or lactation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | King's College London | London | United Kingdom | SE1 9HN |
Sponsors and Collaborators
- King's College London
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRAS 260196