Introduction
Advances in medical management of Crohn’s disease (CD) have improved disease outcomes; however, significant gaps remain. Approximately 30% of patients experience primary non-response to induction therapy with biologics, and over 40% will experience loss of response. There is an urgent need to identify new adjunct therapies, including diet, that can alter the disease course. Dietary patterns characterized by increased intakes of fibre, fruit, vegetables and decreased intakes of processed foods, sugar and omega-6 fatty acids are linked to a reduced prevalence of CD and decreased biomarkers of intestinal and systemic inflammation; however, the effects upon mucosal inflammation are unknown in patients who have lost response to usual medical treatments. We developed the CD Therapeutic Dietary Intervention (CD-TDI), a novel dietary approach incorporating best practices and current evidence to determine its therapeutic potential in reducing inflammation in patients with active CD who have lost response to their usual therapies.
Aims & Methods
This 13-week RCT aimed to explore the efficacy of the CD-TDI compared with conventional management (CM) to reduce clinical disease activity (Harvey-Bradshaw Index (HBI) <5) and reduce mucosal inflammation, as measured by fecal calprotectin (FCP) in mild-to-moderately active luminal CD. Patients with mild to moderately active disease, determined by endoscopic, cross-sectional imaging or FCP >100 ug/g, on stable medical therapy 8 weeks prior to recruitment were eligible to participate (n=28). Upon randomization, the CD-TDI group (n=16) met virtually with a registered dietitian trained in the CD-TDI protocol weekly for 13 weeks. Participants assigned to CM (n=12) followed their habitual diet and met with the same registered dietitian as participants in the CD-TDI group at week 0 (W0) and week 13 (W13) to capture their dietary recall. FCP, HBI, and C-reactive protein (CRP) were assessed at W0 and W13.
Results
Twenty-eight participants (53% females, age 40 years (IQR:31-55); BMI 27 kg/m2 (IQR:24-31)) were enrolled. Medical therapy did not differ between groups, with 54% (15/28) of participants receiving no drug therapy, 29% (8/28) 5-ASA monotherapy, 21% (6/28) biologic therapy, 11% (3/28) corticosteroids or 14% (4/28) immunomodulators. At W0, the FCP, HBI and CRP did not differ significantly between groups. In the CD-TDI group, FCP decreased significantly from 130 ug/g (IQR: 38-411) at W0 to 72 ug/g (IQR:3-153) at W13 (p= 0.01) and significantly differed between the CM group at W13 (p=0.04). In a sub-group analysis (n=11) of participants with FCP >250 ug/g at W0, at W13 the FCP decreased significantly from 632 ug/g (IQR: 356-1013) to 166 ug/g, (IQR:52-701) (p=0.06) within the CD-TDI group, however, this same trend was not observed in the CM (W0:337 ug/g IQR:324-1013 vs. W13:431 ug/g, IQR:46-1770, p=0.69). At W13, between-group differences in the CRP were found between the CD-TDI group (1.0 mg/L, IQR:0.6-2.4) and the CM group (4.5 mg/L, IQR:2.6-13.0) (p=0.002). The CD-TDI group experienced a significant decrease in HBI from W0 to W13 (W0: 3.0, IQR:1.0-5.3; W13: 2.0, IQR:0-3.0; p=0.05), however, this was not observed in the CM group.
Conclusion
At W13, the CD-TDI significantly decreased clinical and biochemical markers of inflammation in patients with mild-to-moderately active CD. This preliminary analysis suggests that CD-TDI could be a potential adjunct management strategy for reducing inflammation in CD. We hope to confirm these promising results with an adequately powered sample.