Randomised clinical trial: the efficacy and safety of propionyl- L-carnitine therapy in patients with ulcerative colitis receiving stable oral treatment

Abstract

Background. Ulcerative colitis (UC) is characterised by impaired fatty-acid oxidation; Lcarnitine has a key role in fatty-acid metabolism and short-chain fatty acids such as butyrate and propionate are important energy source for intestinal epithelial cells. Aim. To evaluate efficacy and safety of colon-release propionyl-L-carnitine (PLC) in patients with mild-to-moderate UC receiving stable oral aminosalicylate or thiopurine therapy. Methods. In a multicentre, phase II, double-blind, parallel-group trial, patients were randomised to receive PLC 1 g ⁄ day, PLC 2 g ⁄ day or placebo. Main inclusion criteria were as follows: age 18–75; disease activity index (DAI) score 3–10 inclusive, be under oral stable treatment with aminosalicylate or thiopurine. The primary endpoint was clinical ⁄ endoscopic response, defined as a decrease in DAI score ‡ 3 points or remission, defined as a DAI score £ 2 with no individual sub-score > 1. Results. Of 121 patients who were randomised, 57 of 79 (72%) patients receiving PLC (combined 1 g and 2 g cohort) had a clinical ⁄ endoscopic response vs. 20 of 40 (50%) receiving placebo (P = 0.02). Specifically, in PLC 1 g ⁄ day group, 30 of 40 (75%) patients had clinical ⁄ endoscopic response (P = 0.02 vs. placebo) and 27 of 39 (69%) in the PLC 2 g ⁄ day group (P = 0.08 vs. placebo). Rates of remission were 22 ⁄ 40 (55%), 19 ⁄ 39 (49%), 14 ⁄ 40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively. PLC had a similar safety profile to placebo; the most common adverse events were gastrointestinal. Conclusion. Propionyl-L-carnitine 1 g ⁄ day should be investigated further as a co-treatment for mild-to-moderate ulcerative colitis (NCT-01026857).