The ADDapt Diet in Reducing Crohn's Disease Inflammation

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 Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Bowel Diseases; Crohn Disease
• Intervention / Treatment: Behavioral: Dietary education

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9HN
    • King's College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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	Proportion of patients achieving faecal calprotectin concentrations <150 µg/g.	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)	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
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
Diet feasibility and acceptability	Acceptability questionnaire, including food-related quality of life	Baseline, 8 weeks and 26 weeks
Faecal calprotectin	Absolute and change in faecal calprotectin concentrations during the trial.	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	Baseline, 8 weeks and 26 weeks
Crohn's Disease Activity Index (CDAI)	Absolute and change in CDAI score during the trial.	Baseline, 8 weeks and 26 weeks
Stool Output	Absolute and change in stool frequency and consistency	Baseline, 8 weeks and 26 weeks
Perceived Crohn's disease control	Absolute and change in score in IBD-control questionnaire	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	Baseline, 8 weeks and 26 weeks
Faecal microbiota composition	Shotgun sequencing	Baseline, 8 weeks and 26 weeks
Faecal microbial gene expression	Meta-transcriptomics	Baseline, 8 weeks and 26 weeks (in a subset of participants)
Dietary intake	Micronutrient and macronutrient intake, food intake and dietary pattern	Baseline, 8 weeks and 26 weeks
Dietary adherence	Reduction in intake of food additives and consumption of study foods and snacks	Baseline, 8 weeks and 26 weeks
Physical Activity	International Physical Activity Questionnaire	Baseline, 8 weeks and 26 weeks
Metabolomics	Metabolomics analyses through Liquid Chromatography - Mass Spectrometry using validated assays.	Baseline and 8 weeks
Biomarker study	Biomarker study through Nuclear Magnetic Resonance Spectroscopy	Baseline and 8 weeks
Genetics	Whole genome single nucleotide polymorphism array genotyping	Baseline

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: Guy's and St Thomas' NHS Foundation Trust; Institut Pasteur; The Leona M. and Harry B. Helmsley Charitable Trust

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Actual): April 25, 2024
• Study Completion (Estimated): August 20, 2024

Study Registration Dates

• First Submitted: July 26, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Dietary intervention
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammation; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: IRAS 260196

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No