P0658Combination of Fecal Microbiota Transplantation and Exclusion Diet for Induction and Maintenance in Mild-to-Moderate Crohn’s Disease: A Randomized Sham-Controlled Trial

Background Faecal microbiota transplantation (FMT) is a promising but unproven therapy for Crohn’s disease (CD). CD Exclusion Diet (CDED) also targets dysbiosis and can induce remission. This RCT evaluated whether combining FMT with CDED improves clinical and endoscopic outcomes in active CD. Methods Adults with mild-to-moderate luminal CD (CDAI 150–450; B1 or non-obstructive B2 phenotype) were enrolled. All participants received CDED and underwent colonoscopy at weeks 0, 2, 6, and 12, and were randomized 1:1 to donor stool (FMT) or saline (sham). Responders at week 12 entered a maintenance phase with repeated 8-weekly FMT or sham infusions plus CDED until week 52. Clinical remission was defined as CDAI <150, response as ≥ 100-point reduction, treatment failure as CDAI rise >70. Endoscopic response required ≥50% SES-CD reduction and remission SES-CD ≤2. Modified intention-to-treat (mITT) analysis performed. Registered at CTRI/2022/10/046861 Results Between 10/2022-09/2024, 35 patients were randomised; 5 were excluded (stricture n = 2, remission at colonoscopy visit n = 2, alternate diagnosis at colectomy n = 1), yielding 30 mITT participants (17 FMT; 13 sham). Mean age was 36.9±11.5 years; 50% were male; baseline CDAI was 189 (IQR 159–243) and SES-CD 14 (IQR 10–18). Disease location was ileocolonic (47%) or colonic (40%), and behavior B1 (63%) or B2 (37%). Three discontinued the study during induction phase(withdrew consent n = 2, pregnancy n = 1). At week 12, clinical remission occurred in 13/17 (76.5%) vs 6/13 (46.2%) (p = 0.13), and clinical response in 9/17 (52.9%) vs 4/13 (30.8%, p = 0.29). Endoscopic remission was achieved in 2/17 (11.8%) vs 1/17 (5.9%) (p = 1.0), and endoscopic response in 4/17 (23.5%) vs 3/17 (17.6%) (p = 1.0). Nineteen responders (FMT 13; sham 6) entered maintenance. Two experienced treatment failure, and 17 completed 52 weeks (FMT 13; sham 4). At week 52, clinical remission was observed in 10/17(58.8%) vs 4/13(30.8%,p = 0.16), and clinical response occurred in 9/17 (52.9%) vs 3/13 (23.1%,p = 0.14). Endoscopic remission occurred in 3/17 (17.6%) vs 0/13 (0%, p = 0.24), and endoscopic response in 8/17 (47.1%) vs 0/13 (0%) (p = 0.004). Combined clinical–endoscopic response was achieved in 7/17 (41.2%) vs 0/13 (0%) (p = 0.01). Among patients not receiving any immunosuppressive or biologic therapy (FMT n = 5; sham n = 3), three in the FMT+CDED arm achieved clinical benefit at 12 weeks and two maintained combined clinical and endoscopic response to 52 weeks, whereas none in the sham arm did. One patient receiving FMT developed liver abscesses requiring antibiotics Conclusion In this first sham-controlled trial of FMT combined with CDED, two-fifths of patients receiving FMT achieved combined clinical–endoscopic response at 52 weeks in mild-moderate active CD Conflict of interest: Arora, Umang: None to disclose Madan, Divya: No conflict of interest Verma, Mahak: No conflict of interest Kumar, Mukesh: I don’t have conflict of interest. Narang, Himanshu: None Kumar, Dr Bipul: No conflict of interest Garg, Rohit: No conflict of interest Monga, Nitika: No conflict of interest Mahajan, Mridul: None Thomas, David: No conflict of interest Mubbunu, Malambo: No conflict of interest Kedia, Saurabh: No conflict of interest Makharia, Govind K: No conflict of interest Ghosh, Tarini: No conflict of interest Prof. Dr. Ahuja, Vineet: This project is part of ICMR grant to IBD center at AIIMS, Delhi