The ADDapt Diet in Reducing Crohn's Disease Inflammation

Not Applicable

Active, not recruiting

• Conditions: Inflammatory Bowel Diseases; Crohn Disease
• Interventions: Behavioral: Dietary education

• Registration Number: NCT04046913
• Lead Sponsor: King's College London

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-07-26
• Study First Submitted QC: 2019-08-02
• Study First Posted: 2019-08-06
• Study Start: 2019-09-09
• Status Verified: 2024-01
• Primary Completion: 2024-04-25
• Last Update Submitted: 2024-06-05
• Last Update Posted: 2024-06-06
• Study Completion: 2024-08-20

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 154

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low food additive diet	Dietary education	Dietary advice, given by a dietitian, will be discussed at trial baseline.
Habitual food additive diet	Dietary education	Dietary advice, given by a dietitian, will be discussed at trial baseline.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Perceived Crohn's disease control	Baseline, 8 weeks and 26 weeks	Absolute and change in score in IBD-control questionnaire
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
Metabolomics	Baseline and 8 weeks	Metabolomics analyses through Liquid Chromatography - Mass Spectrometry using validated assays.
Faecal microbial gene expression	Baseline, 8 weeks and 26 weeks (in a subset of participants)	Meta-transcriptomics
Stool Output	Baseline, 8 weeks and 26 weeks	Absolute and change in stool frequency and consistency
Faecal microbiota composition	Baseline, 8 weeks and 26 weeks	Shotgun sequencing
Biomarker study	Baseline and 8 weeks	Biomarker study through Nuclear Magnetic Resonance Spectroscopy
Genetics	Baseline	Whole genome single nucleotide polymorphism array genotyping
Faecal calprotectin	Baseline, 8 weeks and 26 weeks	Proportion of patients achieving faecal calprotectin concentrations \<150 µg/g.
Physical Activity	Baseline, 8 weeks and 26 weeks	International Physical Activity Questionnaire
Crohn's Disease Activity Index (CDAI)	Baseline and 8 weeks	Proportion of patients achieving ≥100-point reduction in CDAI score by 8 weeks.
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
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

Trial Locations

Locations (1)

King's College London; 🇬🇧 London, United Kingdom