CD-TREAT diet: a novel therapy for active luminal Crohn’s disease
Research type
Research Study
Full title
An open label pilot study of the CD-TREAT diet as a novel therapy for active luminal Crohn’s disease
IRAS ID
223637
Contact name
Richard Hansen
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary
Crohn’s disease (CD) is a chronic inflammatory condition of the gut with severe complications. There is strong evidence to suggest that diet and gut bacteria are key components in the onset, perpetuation and management of CD. An 8-week exclusive liquid diet (EEN) without any normal food is the best treatment for paediatric CD. The mode of action of EEN remains unknown, but according to recent publications of our group, the modulation of the gut bacteria drives its therapeutic properties. While successful, EEN is a challenging therapy to follow. Half of the paediatric EEN patients will require a nasogastric tube to support treatment, its use in adults is limited, and the need for a more palatable diet is very well described. Based on these findings we recently devised a non-liquid and more acceptable dietary treatment, called CD-TREAT diet. CD-TREAT, which is a solid food-based diet designed to replicate the nutrients and food ingredients composition of EEN, was recently tested in healthy adults and a rat model of colitis. In order to pilot CD-TREAT diet as a CD induction treatment we aim to recruit 10 children and 10 adults with active luminal CD. Once consented, we will collect a baseline blood, urine and faecal sample and will prescribe them CD-TREAT for a maximum of 12 weeks. We will also request another 3 blood, urine and faecal samples during these 12 weeks. All the foods/meals of the CD-TREAT diet will be purchased and delivered to the patients’ house by the researcher and the meals which need cooking will be pre-prepared by a sub-contracted catering company. We will measure blood and faecal inflammatory biomarkers, assess the disease activity with routinely used clinical indices and characterise the faecal bacteria and its metabolites.
Summary of Results
The primary aim of this pilot study was to test the ability of CD-TREAT diet to achieve similar clinical response and remission rates, improve baseline blood and gut inflammatory markers, alter the host immunophenotype and improve quality-of-life, in adults and children with active Crohn's Disease (CD) and to compare with outcomes from children whose CD was previously treated with exclusive enteral nutrition (EEN).
In total, 60 participants (adults: n=33, children: n=27) agreed to participate in the study and provided informed consent, of which three subsequently did not meet one of the study eligibility criteria and did not initiate the intervention. All but one (24/25) of the paediatric patients had raised gut inflammatory markers. This was also the case for the majority (25/32, 78%) of adult participants.
Of the 57 participants enrolled in the study, 70% (40) completed the full 8-week treatment with CD-TREAT, 12% (7) discontinued therapy due to treatment failure (no symptom improvement or deterioration) and 18% (10) dropped-out due to issues around diet palatability or interference of the intervention with social interaction and lifestyle.
From our intention to treat analysis (i.e. includes all 57 patients), 54% of all-age patients entered into clinical remission and 60% responded. Proportionally, more children failed treatment, but less dropped out from the intervention compared to adults. Indeed, 40% and 48% of children entered clinical remission and 48% and 52% reported a clinical response after 4- or 8-weeks treatment with CD-TREAT, respectively. Whereas in adults, remission (63% & 59%) and response (69% & 66%) rates were much greater at both 4- and 8-weeks, respectively. 72% of all-age participants indicated a clinical response to treatment, with 66% entering clinical remission after the full 8-weeks of CD-TREAT.
Analysis restricted to the 40 participants (70% of all those enrolled) who completed the full 8- week CD-TREAT diet highlighted all-age remission and response rates of 78% and 85%, respectively, with no significant differences between 4- and 8-weeks of treatment. Alike the intention to treat analysis, remission and response rates were significantly higher in adults than in children. Additionally, the proportion of patients with raised baseline CRP concentrations and low serum albumin levels which normalized following treatment with CD-TREAT increased, however the numbers at baseline and follow-up were too small precluding a statistical power sufficient for statistical analysis. There were no significant changes in body mass index (BMI) nor body weight throughout the intervention.
In participants (n=40) who completed the full 8-week treatment with CD-TREAT, significant improvements in Quality of Life (QoL) scores were observed. This was the case for all domains of the QoL scoring questionnaires, for both paediatric and adult patients, except for the “treatment interventions” and “bowel symptoms” domains of the paediatric IMPACT-III questionnaire.When data for the 40 participants who completed the full CD-TREAT diet were analysed, no statistically significant changes in gut inflammatory marker concentrations (FCAL) were observed following 4- or 8- weeks of treatment. Nonetheless, 56% and 38% of paediatric participants with raised FCAL (>250mg/kg) at enrolment experienced a greater than 50% decrease in FCAL levels after 4- and 8-weeks of treatment, respectively. The same effects were observed, albeit in reduced numbers, in adult participants, whereby 11% and 22% of participants with raised FCAL at study enrolment experienced a greater than 50% decrease in FCAL levels after 4 and 8 weeks of treatment, respectively.
Of the 40 participants who completed the full 8-week treatment, 22 were identified to have a very high likelihood of compliance, as suggested by undetectable levels of gluten in faeces at both 4- and 8-weeks of follow up. In this subset of patients, FCAL (mg/kg) concentrations significantly decreased at 4-weeks and at 8-weeks of treatment. Moreover, 42% and 47% of participants with raised FCAL (>250mg/kg) at enrolment experienced a greater than 50% decrease in FCAL levels after 4- and 8-weeks of treatment, respectively. In contrast, those who were likely to have been compliant with CD-TREAT diet, as indicated by detectable GIP in faeces in at least one of the two follow up time points, observed a statistically insignificant increase in FCAL concentrations.
Participants recorded their habitual diet throughout the intervention using diet diary forms provided to them. In total >2,000 days of dietary data were collected and analysed across all study participants. Food intake records from the 22 participants who displayed high compliance to the intervention were averaged in the preceding 7, 14, and 28 days of the final sample collection at week 8, and subsequently used in machine learning to predict the FCAL response to CD-TREAT. Using artificial intelligence, we developed a model to predict patients who had a decrease in FCAL concentrations of greater than 50% by the end of the 8-week intervention. This model displayed an accuracy of 68% (sensitivity: 78% and specificity: 64%) with results consistent regardless of the timeframe used to assess dietary intake (i.e, 7, 14 or 28 days prior to the end of the intervention). Interestingly, the top three foods which positively predicted a response to CD-TREAT were gluten-free white bread, eggs, and fruit juice. On the contrary, the top three foods which negatively predicted a response to CD-TREAT were apple, tomato, and sugar.
Changes in clinical outcomes were associated with changes in the faecal microbiota and composition. The greater the extent of change in microbiota parameters the better the response to the treatment was.
REC name
West of Scotland REC 1
REC reference
17/WS/0119
Date of REC Opinion
21 Jul 2017
REC opinion
Further Information Favourable Opinion