title: First multicenter study of modified release phosphatidylcholine "LT-02" in ulcerative colitis: a randomized, placebo-controlled trial in mesalazine-refractory courses.
abstract: OBJECTIVE
  Phosphatidylcholine is a key component of the mucosal barrier. Treatment with modified release phosphatidylcholine aims to improve the impaired barrier function. The primary objective is to evaluate the efficacy of LT-02, a newly designed modified release phosphatidylcholine formula, in a multicenter setting.
  
  
  METHODS
  This is a double-blinded, randomized, placebo-controlled, superiority study conducted in 24 ambulatory referral centers in Germany, Lithuania, and Romania. A total of 156 patients with an inadequate response to mesalazine, a disease activity score (Simple Clinical Colitis Activity Index (SCCAI)) of ≥ 5, and bloody diarrhea underwent treatment with 0, 0.8, 1.6, or 3.2 g LT-02. The primary end point was defined a priori as changes in SCCAI from baseline to the end of treatment. The primary statistical model was a general linear least-squares model. The study was funded by the sponsor Lipid Therapeutics, Heidelberg, Germany, and registered at http://clinicaltrials.gov/show/NCT01011322.
  
  
  RESULTS
  Baseline characteristics and dropouts were well balanced between all groups. The primary analyses revealed an SCCAI drop of 33.3% in the placebo group (from 9.0 to 6.0 points) compared with 44.3% in the 0.8 g LT-02 (from 8.8 to 4.9, P>0.05) and 40.7% in the 1.6 g groups (from 8.6 to 5.1, P>0.05). The 3.2 g group improved 51.7% from 8.5 to 4.1 (P=0.030 in comparison with placebo). The remission rate was 15% (6/40) in the placebo group compared with 31.4% (11/35) in the highest LT-02 dose group (P=0.089). Mucosal healing was achieved in 32.5% of placebo patients compared with 47.4% of LT-02 patients (P=0.098); the rates for histologic remission were 20% compared with 40.5%, respectively (P=0.016). There were 17 (48.6%) treatment-emergent adverse events in the highest dose group (and 0 serious adverse events (SAEs)) compared with 22 (55%) in the placebo group (4 SAEs).
  
  
  CONCLUSIONS
  The primary end point analysis showed a statistically significant improvement in disease activity during LT-02 treatment in comparison with placebo. The drug was found to be very safe.
authors.affiliation: 1] Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany [2] Department of Gastroenterology, Viernheim Hospital, Viernheim, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Karner
authors.affiliation: Internistische Facharztpraxis, Luedenscheid, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kocjan
authors.affiliation: Interdisciplinary Crohn & Colitis Center, Frankfurt, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Stein
authors.affiliation: University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: 1] Department of Gastroenterology (Med I), University Hospital Ulm, Ulm, Germany [2] Department of Gastroenterology, Kliniken Landkreis Sigmaringen, Sigmaringen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: von Boyen
authors.affiliation: Internistische Gemeinschaftspraxis, Ludwigshafen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Uebel
authors.affiliation: 1] Clinic for Internal Medicine IV, Department of Gastroenterology and Hepatology, University Hospital Jena, Jena, Germany [2] Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Lithuanian University of Health Sciences, Institute for Digestive Research, Kaunas, Lithuania.
authors.forename: Limas
authors.initials: L
authors.lastname: Kupcinskas
authors.affiliation: 1] SC Endocenter Medicina Integrativa, Bucharest, Romania [2] University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
authors.forename: Ion
authors.initials: I
authors.lastname: Dina
authors.affiliation: Lipid Therapeutics GmbH, Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Zuelch
authors.affiliation: Lipid Therapeutics GmbH, Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Keilhauer
authors.affiliation: Department of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005858:Germany; D006801:Humans; D008097:Lithuania; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D012383:Romania; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010713:Phosphatidylcholines; D010919:Placebos; D019804:Mesalamine