title: Efficacy and safety of the glycine transporter-1 inhibitor org 25935 for the prevention of relapse in alcohol-dependent patients: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Org 25935 is a glycine transporter inhibitor that increases extracellular glycine levels and attenuates alcohol-induced dopaminergic activity in the nucleus accumbens. In animal models, Org 25935 has dose-dependent effects on ethanol intake, preference, and relapse-like behavior without tolerance. The current study aimed to translate these animal findings to humans by examining whether Org 25935 prevents relapse in detoxified alcohol-dependent patients.
  
  
  METHODS
  This was a multicenter, randomized, double-blind, placebo-controlled clinical trial. Adult patients diagnosed with alcohol dependence were randomly assigned to receive Org 25935 12 mg twice a day or placebo for 84 days. The primary end point was percentage heavy drinking days (defined as ≥ 5 standard drinks per day for men and ≥ 4 for women). Secondary end points included other measures of relapse-related drinking behavior (e.g., drinks per day, time to relapse), as well as measures of global functioning, alcohol-related thoughts and cravings, and motivation.
  
  
  RESULTS
  A total of 140 subjects were included in the intent-to-treat analysis. The trial was stopped approximately midway after a futility analysis showing that the likelihood of detecting a signal at study term was <40%. There was no significant difference between Org 25935 and placebo on percentage heavy drinking days or any other measure of relapse-related drinking behavior. Org 25935 showed no safety issues and was fairly well tolerated, with fatigue, dizziness, and transient visual events as the most commonly occurring side effects.
  
  
  CONCLUSIONS
  Org 25935 demonstrated no benefit over placebo in preventing alcohol relapse. Study limitations and implications are discussed.
authors.affiliation: Addiction Biology Unit, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: de Bejczy
authors.forename: Kari R
authors.initials: KR
authors.lastname: Nations
authors.forename: Armin
authors.initials: A
authors.lastname: Szegedi
authors.forename: Joep
authors.initials: J
authors.lastname: Schoemaker
authors.forename: Frank
authors.initials: F
authors.lastname: Ruwe
authors.forename: Bo
authors.initials: B
authors.lastname: Söderpalm
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000175:diagnosis* / Q000188:drug therapy* / Q000517:prevention & control; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention / Q000379:methods; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D050487:Glycine Plasma Membrane Transport Proteins; C520612:N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-ylmethyl)aminomethylcarboxylic acid; C493268:SLC6A9 protein, human; D013764:Tetrahydronaphthalenes
keywords: Alcohol Dependence; Alcohol Relapse Prevention; Glutamate; Glycine Transporter Inhibitor; Org 25935