P1035 The Effects of an Intermittent Reduced Calorie Diet on Crohn’s Disease
Authors: Kulkarni C , Fardeen T , Gubatan J , Jarr K , Dickson E , Jang H , Temby M , Patel A , Singh G , Ye J , Keyashian K , Streett S , Ho E , Barber G , Singh S , Limsui D , Anaizi N , Becker L , Spencer S , Mehrish D , Perelman D , Habtezion A , Sonnenburg J , Gardner C , Sinha S 
Published: January 2025

Abstract

Background
Patient and clinician interest in using diet in inflammatory bowel disease (IBD) is strong, but high-quality data is limited. Cycles of a short intermittent calorie restricted diet (IRCD) have been shown to improve inflammatory and metabolic outcomes in healthy subjects, but how this translates to patients with IBD is unclear. We conducted a randomized control trial to assess the effects of IRCD on disease activity in Crohn’s disease (CD).

Methods
We analyzed data from 97 patients with mild to moderate CD (Crohn’s Disease Activity Index, CDAI 151-450) between the ages of 18-70 years. They were block randomized 2:1 to IRCD and control arms. Patients in the IRCD arm consumed a reduced calorie diet for only 5 consecutive days in a month (1050 calories on day 1, 800 calories for days 2-5) for 3 consecutive months, while patients in the control arm continued their usual diet. Standard of care therapy was continued during the study period. CDAI, short IBD questionnaire (SIBDQ), and patient reported outcomes (PROs) were recorded. The primary endpoint of clinical response was defined as a composite of reduction in CDAI of at least 70 points or a CDAI≤150 at the end of the 3rd 5-day diet cycle. All analyses were done by intention to treat.

Results
Baseline median CDAI was 198 in the IRCD group and 197 in the control arm. Forty-one patients in the IRCD arm (67.2%) and 15 patients in the control arm (44.1%) met the primary endpoint (p=0.03). Thirty-eight patients in the IRCD arm (62.3%) and 12 patients in the control arm (35.3%) achieved clinical remission (CDAI≤150) at the end of the treatment phase (p=0.018). There were no significant changes in ESR or CRP during the study period. In a post-hoc analysis, a significantly higher proportion of participants in the IRCD arm saw a decrease in baseline fecal calprotectin of at least 50% at the end of treatment versus control (p=0.019). Patients in the IRCD arm had a greater response in SIBDQ compared to the control arm at the end of treatment (p=0.01). Thirty-five patients (57.4%) in the IRCD arm and 9 patients in the control group (25.7%) reported remission by PRO (composite of ≤3 BMs/day and abdominal pain ≤1 on a 0-4 scale, p=0.032). Of note, there was no difference in therapy escalation between IRCD and control arms.

Conclusion
There was a significantly greater clinical response in the IRCD arm versus the control arm (p=0.03). A significant difference was also seen in key clinical secondary endpoints in favor of IRCD. The high placebo response rate could be due to several factors including standard of care therapy changes.

References
1.Wei M, Brandhorst S, Shelehchi M, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017;9(377).
2.Gubatan J, Kulkarni CV, Talamantes SM, Temby M, Fardeen T, Sinha SR. Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts. Nutrients. 2023;15(3):579.