P1131A randomised placebo-controlled dietary advice trial of the Four Strategies to SUlphide Reduction (4-SURE) diet in adults with mild-moderately active ulcerative colitis

Abstract Background There is increasing interest in microbial-derived production of hydrogen sulphide (H2S) as a biochemical therapeutic target for ulcerative colitis (UC). This study aimed to determine whether the Four strategies to SUlphide REduction (4-SURE) diet was superior to a Sham diet at inducing clinical and endoscopic response in adults with mild-moderately active UC within 8 weeks. Methods This was a double-blind placebo-controlled trial (ANZCTR 12621001568808). Adults with mild-moderately active UC (Total Mayo 3-10 inclusive of an endoscopic sub score ≥1) on stable therapy were block randomised 1:1 to 4-SURE and Sham dietary advice. The diets were dietitian-taught and nutritionally adequate except differences in key nutrients of interest (fermentable fibres, total and sulphated proteins, food additives). The composite primary endpoint was clinical and endoscopic response (defined as a reduction in Total Mayo score ≥3 inclusive of endoscopic Mayo ≥1) at 8 weeks. Secondary endpoints included clinical response (reduction in partial Mayo ≥2), remission (partial Mayo ≥2), segmental healing (reduction in endoscopic Mayo segmental score ≥1), regression of proximal disease extent (centimeters), histological healing (reduction in Nancy Histology Index ≥1). Adherence was assessed via self-report, 7-day food diaries and faecal H2S concentration. Regression analyses evaluated differences between diets. Results Of 237 screened, 53 commenced 4-SURE (n = 26) and Sham (n = 27) diets. Five withdrew mid-trial (2 4-SURE, 3 Sham). Baseline characteristics were comparable. Four met the primary outcome at 8 weeks (ITT: 15% each diet; p = 0.95; PP 17% each diet; p = 1.00). Clinical response (54% vs 54%; p = 1.00) and endoscopic response (25% vs 21%; p = 0.73) were similar. Segmental healing occurred with both diets (46% vs 42%; p = 0.772). Disease extent regressed by 7.4 (95% CI 0.5-14.2) cm with 4-SURE (p = 0.036) vs 7.2 (0.3-14.0) cm with Sham (p = 0.042) (Fig 1). No serious adverse events occurred. No participant had worsening of disease. Self-reported adherence was equivalent (83% vs 88%) and key nutrients were successfully modified with 4-SURE compared to Sham diet. Faecal H2S reduced by 0.73 (0.19-1.28) mmol/g with 4-SURE (p = 0.009), but not Sham (-0.31 (-0.84, 0.22) mmol/g; p = 0.25). Conclusion The 4-SURE diet achieved its primary biochemical aim, but was not superior to a Sham diet in adults with mild-moderately active UC. Reasons for high rates of segmental healing, disease regression and clinical response within 8 weeks in both arms require further evaluation. Conflict of interest: Dr. Day, Alice: Research Support from The Hospital Research Foundation and Michelle McGrath Fellowship, consultancy fees from Biome Bank, Ferring, AbbVie. Portmann, Laura: No conflict of interest to declare Goodsall, Thomas: Speaker fees from Johnson & Johnson and Abbvie, grant support from Johnson & Johnson Saxon, Sarah: No conflict of interest Mathias, Ryan: Speakers fees from Pfizer, Johnson and Johnson (Janssen), travel grant support from Dr Falk Pharma, Abbvie, consulting fees GPEx Fon, James: No conflict of interest Bibb, Lyndsay: No conflict of interest Uylaki, Wendy: No Conflicts Slater, Rachael: No conflict of interest Young, Remy: No conflict of interest Davis, Rachel: No conflict of interest Bogatic, Damjana: Grants/research funding - BiomeBank, The Gutsy Group Edwards, Suzanne: No conflicts Joyce, Paul: No conflict of interest Yao, Ck: I have received research support for investigator-initiated studies from Gastroenterological Society of Australia, International Organisation for the Study of IBD, Crohn’s Colitis Australia and Atmo Biosciences and travel honoraria from Yakult Australia, Viatris and Dr Falk Pharma. My department, the Department of Gastroenterology, Monash University receives royalties from the sales of digital apps, online education course on the FODMAP diet. No personal renumeration is received. Wheeler, Reuben: No conflict of interest Forster, Samuel: No conflict of interest Costello, Samuel: Employee: BiomeBank Shareholder: BiomeBank, Microbiotica Research funds and speakers fees: Janssen, Ferring, MSD, Microbiotica Probert, Christopher: Nothing to declare Gibson, Peter: No conflict of interest Bryant, Robert Venning: Robert V. Bryant has received grant/research support/speaker honoraria/advisory board fees from AbbVie, Ferring, Janssen, Shire, Takeda, GlaxoSmithKline, Bristol Myers Squibb, and Emerge Health and is a shareholder in Biomebank.