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

• Published in: Alimentary pharmacology & therapeutics Vol. 34; no. 9; pp. 1088 - 1097
• Main Authors: Mikhailova, T. L., Sishkova, E., Poniewierka, E., Zhidkov, K. P., Bakulin, I. G., Kupcinskas, L., Lesniakowski, K., Grinevich, V. B., Malecka‐Panas, E., Ardizzone, S., D’Arienzo, A., Valpiani, D., Koch, M., Denapiene, G., Vago, G., Fociani, P., Zerbi, P., Ceracchi, M., Camerini, R., Gasbarrini, G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2011; Blackwell
• Subjects: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Carnitine - administration & dosage; Carnitine - adverse effects; Carnitine - analogs & derivatives; Cohort Studies; Colitis, Ulcerative - drug therapy; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Young Adult
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2011.04844.x

Aliment Pharmacol Ther 2011; 34: 1088–1097 Summary Background  Ulcerative colitis (UC) is characterised by impaired fatty‐acid oxidation; l‐carnitine 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).