The ADDapt diet in reducing Crohn's disease inflammation
| ISRCTN | ISRCTN14054186 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14054186 |
| ClinicalTrials.gov number | NCT04046913 |
| Secondary identifying numbers | CPMS 41991 |
- Submission date
- 29/07/2019
- Registration date
- 29/07/2019
- Last edited
- 17/10/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
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 16 years or older (updated 03/02/2022, previously: 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 December 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?
Dr Aaron Bancil
aaron.bancil@kcl.ac.uk
Contact information
Scientific
King's College London
4.103 Franklin Wilkins Building
150 Stamford Street
London
SE1 9NH
United Kingdom
| Phone | +44 (0)207 848 4552 |
|---|---|
| aaron.bancil@kcl.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Dietary |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Quality of life |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | The ADDapt diet in reducing Crohn's disease inflammation |
| Study 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(s) | 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 |
| Condition | Crohn's disease |
| Intervention | Current intervention as of 03/02/2022: 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. Further trusts have been added recently. 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). ______ Previous 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 |
| 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 study start date | 01/01/2019 |
| Overall study end date | 31/12/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 154; UK Sample Size: 154 |
| Total final enrolment | 154 |
| Participant inclusion criteria | Current participant inclusion criteria as of 03/02/2022: 1. Adults aged ≥16 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 _____ Previous 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 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 | 29/02/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Great Maze Pond
London
SE1 9RT
United Kingdom
Harrow
HA1 3UJ
United Kingdom
London
NW1 2BU
United Kingdom
London
NW3 2QG
United Kingdom
Whitechapel
London
E1 1BB
United Kingdom
369 Fulham Road
London
SW10 9NH
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
North Manchester General Hospital
Delaunays Road, Crumpsall
Manchester
M8 5RB
United Kingdom
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom
Marlborough Street
Bristol
BS2 8HW
United Kingdom
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Leeds General Infirmary
Great George St
Leeds
LS1 3EX
United Kingdom
Edinburgh
EH4 2XU
United Kingdom
St Leonards-on-Sea
TN37 7RD
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Wolverhampton
WV10 0QP
United Kingdom
London
SE5 9RS
United Kingdom
Praed Street
London
W2 1NY
United Kingdom
Southampton
SO16 6YD
United Kingdom
Sponsor information
University/education
King's College London
Room 5.31 James Clerk Maxwell Building
57 Waterloo Road
London
SE1 8WA
England
United Kingdom
| Phone | +442078483224 |
|---|---|
| reza.razavi@kcl.ac.uk | |
"ROR" |
https://ror.org/0220mzb33 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Helmsley Charitable Trust, The Leona M. and Harry B. Helmsley Charitable Trust, Leona M. & Harry B. Helmsley Charitable Trust, The Helmsley Charitable Trust
- Location
- United States of America
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 28/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
17/10/2024: The following changes were made to the trial record:
1. The total final enrolment was added.
2. The intention to publish date was changed from 01/09/2024 to 28/02/2025.
02/01/2024: The following changes have been made:
1. The recruitment end date was changed from 30/09/2023 to 29/02/2024.
2. The overall study end date was changed from 01/01/2024 to 31/12/2024.
3. The intention to publish date was changed from 15/07/2022 to 01/09/2024.
4. The study participating centres were updated to remove Royal Surrey County Hospital and add NHS Lothian, East Sussex Healthcare NHS Trust, Royal Devon and Exeter NHS Foundation Trust, The Royal Wolverhampton NHS Trust, King's College Hospital NHS Foundation Trust, Imperial College Healthcare NHS Trust and University Hospital Southampton NHS Trust Foundation Trust.
03/02/2022: The following changes have been made:
1. The intervention has been updated.
2. The participant inclusion criteria have been updated and the plain English summary has been updated accordingly.
3. The recruitment end date has been changed from 30/11/2021 to 30/09/2023.
4. The trial participating centres "Chelsea and Westminster Hospital NHS Foundation Trust", "Addenbrookes Hospital", "Pennine Acute Hospitals NHS Trust", "County Durham and Darlington NHS Foundation Trust", "University Hospital Bristol", "The Newcastle upon Tyne Hospitals NHS Foundation Trust", "United Leeds Teaching Hospital NHS Trust", and "Royal Surrey County Hospital" has been added.
08/07/2021: The following changes have been made:
1. The recruitment end date has been changed from 15/07/2021 to 30/11/2021.
2. The ClinicalTrials.gov number has been added.
3. The trial contact has been updated and the plain English summary has been updated to reflect this change.
30/07/2019: Internal review.
29/07/2019: Trial’s existence confirmed by National Institute for Health Research (NIHR)
