A Crohn’s disease exclusion diet (CDED) plus partial enteral nutrition (PEN) yielded sustained remission in a randomized controlled study of children with mild to moderate Crohn’s, according to Israeli and Canadian researchers.
The diet was also better tolerated than exclusive enteral nutrition (EEN) and inflammation markers were lower in those on CDED/PEN.
At week 6, a total of 30 of 40 children (75%) given CDED plus PEN were in corticosteroid-free remission versus 20 of 34 children (59%) given EEN (P=0.38), reported Johan Van Limbergen, MD, PhD, of Dalhousie University in Halifax, Nova Scotia, and colleagues in Gastroenterology.
At week 12, 28 of 37 children (75.6%) given CDED plus PEN were in corticosteroid-free remission compared with 14 of 31 children (45.1%) receiving EEN and then PEN (P=0.01). The odds ratio for remission in children receiving CDED plus PEN was 3.77 (95% CI 1.34-10.59).
“In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein [CRP] and fecal level of calprotectin) and fecal Proteobacteria,” Van Limbergen and colleagues wrote. “These data support the use of CDED+PEN as a first-line therapy for children with luminal mild to moderate active CD, and warrant further study to explore the role of diet in conjunction with drugs to optimize therapy in [Crohn’s] patients.”
During 2013-2018, the 12-week prospective trial of dietary tolerance enrolled 78 children ages 4 to 18 at 12 clinics in Israel and Canada. Patients had a pediatric Crohn’s disease activity index (PCDAI) score of 10 to 40 and evidence of active inflammation such as elevated CRP over 5 g/L, an erythrocyte sedimentation rate over 20 mm/h, or calprotectin over 200 μg/g. within 36 months of diagnosis.
Participants were randomly assigned to CDED – a whole-foods regimen designed to reduce exposure to dietary components with adverse effects on the microbiome and intestinal barrier – with 50% of calculated energy requirement derived from a special formula (Modulen, Nestlé) for 6 weeks.
In a second stage of the study from weeks 7 through 12, CDED was combined with 25% PEN in 40 children (group 1). A second group of 38 children received EEN for 6 weeks followed by a gradually introduced table-food diet with 25% PEN from weeks 7 to 12.
Both groups were exposed to PEN plus a free diet by week 12.
Four patients withdrew due to intolerance by 48 hours, leaving 74 patients, mean age of 14.2 ± 2.7 years, for remission analysis.
Patients were evaluated at baseline and at weeks 3, 6, and 12. In addition to laboratory tests, 16S rRNA gene (V4V5) sequencing was performed on stool samples.
The primary endpoint was dietary tolerance, with secondary endpoints of intention to treat (ITT) remission at week 6 (PCDAI score below 10) and corticosteroid-free ITT sustained remission at week 12.
The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%, P=o.002), Limbergen and co-authors reported. The odds ratio for tolerance of CDED and PEN was 13.92 (95% CI 1.68-115.14).
As the authors pointed out, although EEN is recommended for children with mild-to-moderate Crohn’s, it is challenging to implement and maintain. Furthermore, after an EEN regimen, as many as one half of patients will have an early clinical flare when they resume an unrestricted oral diet, so better tolerated alternatives are under active study. Last year, MedPage Today reported on preliminary Scottish research suggesting that an ordinary whole-foods diet could achieve the same effect in the gastrointestinal GI tract as EEN.
Van Limbergen and colleagues concluded that with CDED better tolerated than EEN, more effective in inducing remission, and yielding changes in the fecal microbiome associated with remission, CDED plus PEN is an option for inducing remission in children with mild to moderate CD.
Asked for her perspective, Deborah A. Goldman, MD, of Cleveland Clinic Children’s department of pediatric gastroenterology, who was not involved with the study, said this exclusion diet, which has been well studied, offers a better option for pediatric patients: “They can still eat some foods that they enjoy, such as eggs, chicken, potatoes, apples, and mashed bananas, along with the drink, which is quite well tolerated.”
At the same time, she continued, children can thus avoid the potential triggers of intestinal dysbiosis that abound in other typical Western diets, including a high wheat intake and high dairy consumption. Fish, rice, and other fruits and vegetables can then be gradually introduced while preventing the Crohn’s disease recurrence that happens after discontinuing EEN.
“This diet has a lot of promise and offers a wonderful opportunity for children to try nutritional therapy,” said Goldman, who noted that she is undertaking training in the details of the diet to use in her clinic, where EEN is currently available.
Limitations of the study, the researchers said, include its use of two central laboratories for assessing calprotectin and the lack of direct assessment of mucosal healing by endoscopy.
The study was funded in Israel by the Azrieli Foundation and Nestlé Health Science, which provided Modulen to participating sites. In Canada, the study was supported by local divisional funds, the Women and Children’s Health Research Institute and the Canadian Institutes of Health Research.
Van Limbergen and several co-authors disclosed financial ties to various private-sector companies, including Nestlé, AbbVie, and Janssen.
Goldman reported having no relevant competing interests with regard to her comments.