Comparing Two Diets to Decrease Symptoms from Crohn's Disease – The DINE-CD Study [Internet]

Background: Crohn disease (CD) is a chronic, relapsing form of inflammatory bowel disease for which there is no known cure. Chronic immunosuppressive therapy is the main therapeutic approach. Many patients with mild to moderate symptoms are interested in alternatives to chronic immunosuppressive therapy, such as therapeutic diets. Existing evidence supports the therapeutic potential of the Mediterranean diet (MD) and the specific carbohydrate diet (SCD) as treatment for mild to moderately active CD; however, the most effective therapeutic diet for CD has not been established.

Objectives: The Diet to INducE Remission in Crohn's Disease (DINE-CD) study was designed to compare the effectiveness of the MD vs the SCD for treatment of patients with CD who have mild to moderate symptoms.

Methods: The DINE-CD study was a multicenter, randomized, comparative effectiveness trial of the MD vs the SCD. The study included adult patients with CD who had mild to moderate symptoms—that is, a short Crohn's Disease Activity Index (sCDAI) score of 176 to 399. Patients were randomly assigned 1:1, stratified by use of biologic medications, to follow either the MD or the SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, they were instructed to follow the diet independently and were given an option to purchase prepared meals. The primary outcome was symptomatic remission (sCDAI score <150) at week 6. Secondary outcomes included symptomatic remission at week 12 and the following factors, assessed at weeks 6 and 12: clinical remission based on a composite of symptoms, examination findings, and laboratory studies using the full CDAI (CDAI score <150); fecal calprotectin (FC) response (FC <250 μg/g and reduction by >50% from baseline among those with baseline FC >250 μg/g); C-reactive protein (CRP) response (high-sensitivity CRP [hsCRP] <5 mg/L and >50% reduction from baseline among those with hsCRP >5 mg/L); and scores on the short Inflammatory Bowel Disease Questionnaire (SIBDQ) and Patient-Reported Outcomes Measurement Information System (PROMIS) measures of fatigue, pain, sleep, and social isolation. Comparisons between groups were made using the Cochran-Mantel-Haenszel χ² test or t test and, within groups, the paired t test.

Results: A total of 194 patients were randomly assigned, but because of an error, 3 participants had a baseline sCDAI score <150 and were excluded from the effectiveness analyses (n = 92 assigned to MD and n = 99 assigned to SCD). Elevated FC, CRP, or inflammation at endoscopy was confirmed at screening in 46% (38 MD; 50 SCD) of participants. Before week 6, 2 participants in the MD group and 3 participants in the SCD group were lost to follow-up. Twelve and 15 participants in the MD and SCD groups, respectively, withdrew from the study before week 6. Within the MD and SCD groups, from week 0 to week 6, there was improvement in the mean [SD] sCDAI score in the MD group (−59.33 [64.53]; P < .0001) and the SCD group (−71.78 [75.94]; P < .0001). However, the magnitude of change did not differ between the treatment groups (P = .23). The percentage of participants who achieved symptomatic remission at week 6 did not differ by diet (43.5% on the MD and 46.5% on the SCD; P = .77). Clinical remission was achieved in 47.8% of patients on the MD and 48.5% of patients on the SCD (P = .93). FC response was achieved in 4 participants (30.8%) on the MD and 8 participants (34.8%) on the SCD (P = .83). CRP response was achieved in only 1 participant (3.6%) on the MD and 2 participants (5.4%) on the SCD (P = .68). At week 12, the percentage of participants who achieved symptomatic remission was 40.2% with the MD and 42.4% with the SCD (P = .87). There was no evidence of heterogeneity of response based on the presence or absence of confirmed inflammation at screening for the primary outcome (test for interaction, P = .68). Adherence to the diet all the time at week 6 of the study was reported by 59 (64%) of those on the MD and 67 (68%) of those on the SCD. By week 12, 39 participants (42%) and 40 participants (40%) reported adherence all the time to the MD and SCD, respectively.

Conclusions: Symptomatic remission was achieved in ≥40% of participants on both diets regardless of confirmed inflammation. CRP response was uncommon. None of the effectiveness measures were significantly different by treatment group.

Limitations: Despite being provided with meals and snacks per their assigned diet for the first 6 weeks of the study, <70% of participants reported attempting to adhere to either the MD or the SCD all the time.