The ADDapt Diet in Reducing Crohn's Disease Inflammation

King's College London154 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

154

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: Difference between baseline and week 8

Secondary Outcomes

Faecal calprotectin

The proportion of patients achieving at least a 50% reduction in faecal calprotectin concentration.

Time frame: Baseline, 8 weeks and 26 weeks

Faecal calprotectin

Absolute and change in faecal calprotectin concentrations during the trial.

Time frame: Baseline, 8 weeks and 26 weeks

Faecal calprotectin

Proportion of patients achieving faecal calprotectin concentrations \<150 µg/g.

Time frame: Baseline, 8 weeks and 26 weeks

Serum C-reactive protein

Absolute and change in CRP concentration and proportion of patients achieving a CRP concentration \<5 mg/L

Time frame: Baseline, 8 weeks and 26 weeks

Mucosal immune cell gene expression

RNA sequencing on GI immune cells isolated from rectal biopsies

Time frame: Baseline and 8 weeks

Crohn's Disease Activity Index (CDAI)

Absolute and change in CDAI score during the trial.

Time frame: 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.

Time frame: Baseline and 8 weeks

Crohn's Disease Activity Index (CDAI)

Proportion of patients achieving ≥100-point reduction in CDAI score by 8 weeks.

Time frame: Baseline and 8 weeks

Stool Output

Absolute and change in stool frequency and consistency

Time frame: Baseline, 8 weeks and 26 weeks

Perceived Crohn's disease control

Absolute and change in score in IBD-control questionnaire

Time frame: Baseline, 8 weeks and 26 weeks

Health related quality of life

Absolute and change in Inflammatory Bowel Disease questionnaire (IBDQ) score, and proportion of patients achieving clinical remission i.e., IBDQ score \>168

Time frame: Baseline, 8 weeks and 26 weeks

Faecal microbiota composition

Shotgun sequencing

Time frame: Baseline, 8 weeks and 26 weeks

Faecal microbial gene expression

Meta-transcriptomics

Time frame: Baseline, 8 weeks and 26 weeks (in a subset of participants)

Mucosal microbiota composition

16S sequencing

Time frame: Baseline and 8 weeks (in a subset of participants)

Gastrointestinal permeability

Sugar probe solution urinary analysis to determine intestinal permeability

Time frame: Baseline and 8 weeks

Dietary intake

Micronutrient and macronutrient intake, food intake and dietary pattern

Time frame: Baseline, 8 weeks and 26 weeks

Dietary adherence

Reduction in intake of food additives and consumption of study foods and snacks

Time frame: Baseline, 8 weeks and 26 weeks

Diet feasibility and acceptability

Acceptability questionnaire, including food-related quality of life

Time frame: Baseline, 8 weeks and 26 weeks

Physical Activity

International Physical Activity Questionnaire

Time frame: Baseline, 8 weeks and 26 weeks

Metabolomics

Metabolomics analyses through Liquid Chromatography - Mass Spectrometry using validated assays.

Time frame: Baseline and 8 weeks

Biomarker study

Biomarker study through Nuclear Magnetic Resonance Spectroscopy

Time frame: Baseline and 8 weeks

Genetics

Whole genome single nucleotide polymorphism array genotyping

Time frame: Baseline

The ADDapt Diet in Reducing Crohn's Disease Inflammation

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes