Condition category
Digestive System
Date applied
29/07/2019
Date assigned
29/07/2019
Last edited
30/07/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
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.

Who can participate?
Adults aged 18 years or older with mildly active Crohn's disease.

What does the study involve?
Patients will be asked to follow a set diet for 8-weeks, during which time they will attend clinic visits to gather information on food intake, general health, and to provide samples for analysis.

What are the possible benefits and risks of participating?
The results of this study may help to answer scientific questions about whether reducing specific food ingredients improves intestinal inflammation in patients with active Crohn’s disease, and whether there is any beneficial effect on the gut bacteria. The ADDapt diet can be challenging to follow because certain pre-prepared and convenience foods are excluded. There are still plenty of convenience foods, pre-prepared foods and ready-meals that are suitable, and these can still be eaten provided you check their suitability with the dietitian. The ADDapt diet is nutritionally balanced and your dietitian will be able to help answer any questions you have whilst you are on the diet. If you are preparing food for other people, it is safe for them to eat the same meals as you.

Where is the study run from?
King's College, London

When is the study starting and how long is it expected to run for?
July 2019 to January 2024

Who is funding the study?
1. Leona M. and Harry B. Helmsley Charitable Trust
2. National Institute for Health Research (NIHR), UK

Who is the main contact?
Alicia Sandall
alicia.sandall@kcl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Miss Alicia Sandall

ORCID ID

Contact details

King's College London
4.103 Franklin Wilkins Building
150 Stamford Street
London
SE1 9NH
United Kingdom
+44 (0)207 848 4552
Alicia.sandall@kcl.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

41991

Study information

Scientific title

The ADDapt diet in reducing Crohn's disease inflammation

Acronym

ADDapt

Study hypothesis

There is a difference in the proportion of patients achieving at least a 70 point reduction in the Crohn's Disease Activity Index (CDAI) between baseline and end of the trial, between the two diet groups.

Ethics approval

Approved 15/07/2019, East of Scotland Research Ethics Service (EoSRES) (Tayside medical Science Centre, Residency Block Level 3. George Pirie Way, Ninewells Hospital and Medical School, Dundee, DD1 9SY; +441382383878; eosres.tayside@nhs.net), ref: 19/ES/0049

Study design

Randomised; Interventional; Design type: Treatment, Dietary

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Quality of life

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Crohn's disease

Intervention

This will be an 8-week randomised double-blind, placebo-controlled trial in 154 patients with mildly active, stable Crohn's disease. Patients will be recruited from five London inflammatory bowel disease (IBD) centres.
These will be Guy's and St Thomas' NHS Foundation Trust, Barts Health NHS Trust, St Marks Hospital, University College Hospital NHS Foundation Trust and Royal Free Hospital NHS Foundation Trust.

In this trial, all patients will follow a low food additive background diet. Patients will be randomised to either the low food additive diet or control diet (mimicking a habitual UK diet) group, in a 1:1 ratio. Block randomisation will be stratified according to Crohn’s Disease location (ileal, ileo-colonic, colonic) and whether the patient opts for sigmoidoscopy or not. The randomisation schedule will be constructed using an online program by a researcher not involved in trial planning or recruitment. The researcher randomising participants and measuring trial outcomes will not be aware of diet allocation.

In addition to following the background low food additive diet, patients in the diet groups will receive the following foods:
Low food additive diet (intervention) group:
- Additive-free trial foods formulated specifically for this project, to be eaten in specific portions every day during the trial.
Control group:
- A supply of food additive-containing trial foods formulated specifically for this project.

Trial procedures:

Screening:
Trial investigators will attend gastroenterology clinics at each of the five recruitment sites each week. Gastroenterologists, IBD nurses and IBD pharmacists will refer potentially suitable and willing patients for screening. Patients will be given a participant information sheet (PIS) and offered their hospital's leaflet on sigmoidosopies and will be screened against inclusion and exclusion criteria. Patients will be given at least 24 hours to consider the study and ask questions prior to consent.
Suitable patients wishing to take part will be allowed to consent to the trial on the day of screening if this is more convenient for them than attending a separate consent visit. Otherwise, patients will attend the hospital clinic or the metabolic research unit at King's College London to provide consent.
After consent, eligible patients will be instructed by an experienced research dietitian to complete a 7-day food and symptom diary, which will be used to assess disease activity and dietary intake.

Baseline visit:
Patients meeting all of the inclusion criteria and none of the exclusion criteria and having consented will attend a baseline visit at either the hospital clinic or the metabolic research unit at King's College London (whichever is most convenient for the patient) following an overnight fast. The following procedures will be undertaken:
• Demographic characteristics
• Patient-completed questionnaires
• A whole stool sample will be collected within 2 hours of the visit
• A baseline urine sample will be collected for intestinal permeability
• Blood samples will be collected
• Participants opting into the sigmoidoscopy sub study (n=77) will undergo an unprepared flexible sigmoidoscopy
• All participants will be provided with thorough instruction on the low food additive diet by an experienced specialist dietitian.
Patients will be randomized to either the low food additive diet or control diet and will receive a supply of the foods described above.

Monitoring and safety: Patients will be given contact details for the study investigators and will be telephoned once a week to monitor progress with the intervention, compliance to the low food additive diet and consumption of the trial foods. Furthermore, any reported adverse events will be recorded at these contacts, and investigators will address any concerns that patients may have regarding any aspects of the trial.
Compliance: Compliance with the experimental diet allocation and the trial foods will be monitored and encouraged at the weekly telephone contacts.
Follow-up visit: After the 8-week trial, participants will return for an end of trial visit after an overnight fast. Participants will complete a food and symptom diary, identical to that completed during screening, for 7 days prior to this visit. At this visit, the following will take place:
• The Crohn's Disease Activity Index (CDAI) score will be calculated
• Stool, urine and blood samples will be collected using the methods described in the baseline visit. Flexible, unprepared sigmoidoscopies will be performed as described in the baseline visit

Long-term follow-up:
Following completion of the 8-week trial, patients will have the option of continuing to follow the experimental diet for an additional 16 weeks. At monthly intervals during this period, a telephone visit will be conducted, to investigate diet compliance and acceptability and to provide patient support.
At the end of trial visit (following the 8-week trial), patients will be provided with a blank 7-day food and symptom diary and will be instructed to complete it for the 7 days prior to a long-term visit, which will take place after a total of 24 weeks

At the long-term visit, the following procedures will take place:
• CDAI score will be calculated
• Patient-completed questionnaires
• A whole stool sample and blood samples will be collected using the methods described above.
Following completion of the trial (or withdrawal), patients will be instructed to return to their normal diet and will be provided with written general dietary guidance for Crohn's disease (Crohn’s and Colitis UK).

Intervention type

Other

Phase

Drug names

Primary outcome measure

Reduction in the Crohn’s Disease Activity Index (CDAI) between baseline and end of trial (8-weeks)

Secondary outcome measures

1. Crohn’s disease activity as measured using the Crohn’s Disease Activity Index (CDAI) at baseline, week 8 and week 26
2. Gastrointestinal inflammation as measured using faecal calprotectin at baseline, week 8 and week 26
3. Systemic inflammation as measured using CRP concentration at baseline, week 8 and week 26
4. Perceived disease control as measured by the IBD-control questionnaire at baseline, week 8 and week 26
5. Health related quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBD-Q) at baseline, week 8 and week 26.
6. Dietary intake as measured by 7-day food diaries at baseline, week 8 and week 26
7. Dietary compliance and acceptability as measured by acceptability questionnaire and food-related Quality of Life questionnaire at baseline, week 8 and week 26
8. Gastrointestinal permeability as measured by urine analysis at baseline and week 8
9. Gastrointestinal microbiota as measured by faecal microbiota composition and mucosal microbiota composition at baseline and week 8 (in a subset of participants)
10. Mucosal immune gene expression as measured on immune cells from rectal biopsies at baseline and week 8 (in a subset of participants)

Overall trial start date

01/01/2019

Overall trial end date

01/01/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adults aged > = 18 years
2. Crohn's disease diagnosis (defined by standard clinical, histological and radiological criteria) of at least 6 months
3. Mildly active disease as defined by:
3.1 Defined by physician assessment that no change in medication is required
3.2 Faecal calprotectin > 150 µg/g
3.3 CDAI between 150-250
3.4 Current body weight of > = 50 kg
3.5 Individuals able to give informed consent and willingness to participate

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 154; UK Sample Size: 154

Participant exclusion criteria

1. 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.
2. Used rectal 5-ASA or rectal steroids in the preceding 4 weeks
3. Previous extensive bowel resection, defined as having had > 2 intestinal resections, a sub-total colectomy or documented short bowel syndrome
4. Poorly controlled bile acid malabsorption
5. Current stoma
6. Recent use of the following treatments: antibiotics, probiotics, prebiotic or fibre supplements in the preceding four weeks, NSAIDs during the preceding week
7. Full bowel preparation for a diagnostic procedure in preceding 4 weeks
8. 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
9. Exclusive enteral nutrition in the past 8 weeks
10. Assessed as at nutritional risk, as defined by any of the following:
10.1 BMI < = 18.5 kg/m2
10.2 Previous or current eating disorder
10.3 Currently receiving prescribed oral nutritional supplements
11. Following a restrictive diet (e.g. multiple restrictions due to numerous self-reported allergies) as judged by the dietitian
12. Reported pregnancy or lactation

Recruitment start date

12/08/2019

Recruitment end date

15/07/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Guy’s Hospital
Guy’s & St Thomas’ NHS Foundation Trust Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Northwick Park Hospital
Watford Road
Harrow
HA1 3UJ
United Kingdom

Trial participating centre

University College London Hospitals NHS Foundation Trust
235 Euston Road
London
NW1 2BU
United Kingdom

Trial participating centre

Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

The Royal London Hospital
Whitechapel Road Whitechapel
London
E1 1BB
United Kingdom

Sponsor information

Organisation

King's College London

Sponsor details

King's College London
Room 5.31 James Clerk Maxwell Building
57 Waterloo Road
London
SE1 8WA
United Kingdom
+442078483224
reza.razavi@kcl.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Leona M. and Harry B. Helmsley Charitable Trust

Alternative name(s)

Helmsley Charitable Trust

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

United States of America

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date

Intention to publish date

15/07/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

30/07/2019: Internal review. 29/07/2019: Trial’s existence confirmed by National Institute for Health Research (NIHR)