Trial of trefoil factor 3 enemas, in combination with oral 5-aminosalicylic acid, for the treatment of mild-to-moderate left-sided ulcerative colitis.

Author(s): Mahmood A, Melley L, Fitzgerald AJ, Ghosh S, Playford RJ

Affiliation(s): Department of Gastroenterology, Imperial College, Hammersmith Hospital Campus, London, UK.

Publication date & source: 2005-06-01, Aliment Pharmacol Ther., 21(11):1357-64.

Publication type: Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Randomized Controlled Trial

BACKGROUND: Current treatment of ulcerative colitis is imperfect. Trefoil peptides are known to stimulate repair in many models of injury, including animal models of colitis. AIM: To assess the efficacy of trefoil factor family-3 enema treatment in a clinical trial. METHODS: A total of 16 patients with mild-to-moderate left sided ulcerative colitis were recruited into a double-blind randomized placebo-controlled study. Patients taking steroids or with proctitis only were excluded. Patients received 75 mL enemas containing either human recombinant trefoil factor family-3 (10 mg/mL) or saline alone once a day for 14 days. All patients also received an oral dose-increment of 1.2 g of mesalazine daily above their normal usage. Patients were assessed at 0, 2, 4 and 12 weeks. Remission was defined as Ulcerative Colitis Disease Activity Index of 0 or 1 with no blood in stool. Individual clinical improvement was defined as a Ulcerative Colitis Disease Activity Index reduction of >3. Data was analysed using chi-square test and anova. RESULTS: Median Ulcerative Colitis Disease Activity Index at entry were 8.5 (trefoil factor family-3 group) and 8 (placebo group). Analysed on an intention-to-treat basis, only one patient went into remission (in trefoil factor family-3 group at day 28). Clinical improvement was seen in two trefoil factor family-3 and three placebo patients on day 14 and two patients in each group on day 28. CONCLUSION: Increasing the dose of 5-aminosalicylic acid was moderately effective in reducing the Ulcerative Colitis Disease Activity Index but was insufficient to induce remission. Trefoil factor family-3 enemas were well-tolerated but did not provide additional benefit above that of adding additional 5-aminosalicylic acid alone.