title: The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  We investigated the effects of the fatty acid-bile acid conjugate 3β-arachidyl-amido, 7α-12α-dihydroxy, 5β-cholan-24-oic acid (Aramchol; Trima Israel Pharmaceutical Products Ltd, Maabarot, Israel) in a phase 2 trial of patients with nonalcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  We performed a randomized, double-blind, placebo-controlled trial of 60 patients with biopsy-confirmed NAFLD (6 with nonalcoholic steatohepatitis) at 10 centers in Israel. Patients were given Aramchol (100 or 300 mg) or placebo once daily for 3 months (n = 20/group). The main end point was the difference between groups in the change in liver fat content according to magnetic resonance spectroscopy. The secondary end points focused on the differences between groups in alterations of liver enzyme levels, levels of adiponectin, homeostasis model assessment scores, and endothelial function.
  
  
  RESULTS
  No serious or drug-related adverse events were observed in the 58 patients who completed the study. Over 3 months, liver fat content decreased by 12.57% ± 22.14% in patients given 300 mg/day Aramchol, but increased by 6.39% ± 36.27% in the placebo group (P = .02 for the difference between groups, adjusted for age, sex, and body mass index). Liver fat content decreased in the 100-mg Aramchol group, by 2.89% ± 28.22%, but this change was nonsignificant (P = .35), indicating a dose-response relationship (P for trend = .01). Groups given Aramchol had nonsignificant improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin, but homeostasis model assessment scores did not change. The appropriateness of a single daily dose was confirmed by pharmacokinetic analysis.
  
  
  CONCLUSIONS
  Three months' administration of the fatty acid-bile acid conjugate Aramchol is safe, tolerable, and significantly reduces liver fat content in patients with NAFLD. The reduction in liver fat content occurred in a dose-dependent manner and was associated with a trend of metabolic improvements, indicating that Aramchol might be used for the treatment of fatty liver disease. ClinicalTrials.gov number: NCT01094158.
authors.affiliation: Liver and Gastroenterology Unit, Division of Medicine, Hadassah University Medical Center, Jerusalem, Israel; Holy Family Hospital, Nazareth, Israel. Electronic address: safadi@hadassah.org.il.
authors.forename: Rifaat
authors.initials: R
authors.lastname: Safadi
authors.affiliation: Department of Gastroenterology and Hepatology, University of Tel Aviv, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Fred M
authors.initials: FM
authors.lastname: Konikoff
authors.affiliation: Holy Family Hospital, Nazareth, Israel.
authors.forename: Mahmud
authors.initials: M
authors.lastname: Mahamid
authors.affiliation: Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel; School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Zelber-Sagi
authors.affiliation: Galmed Medical Research, Limited, Tel-Aviv, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Halpern
authors.affiliation: Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel; Galmed Medical Research, Limited, Tel-Aviv, Israel.
authors.forename: Tuvia
authors.initials: T
authors.lastname: Gilat
authors.affiliation: Liver and Gastroenterology Unit, Division of Medicine, Hadassah University Medical Center, Jerusalem, Israel; Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Oren
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002793:Cholic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005223:Fats / Q000032:analysis*; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007557:Israel; D008099:Liver / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D010920:Placenta; D011247:Pregnancy; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002793:Cholic Acids; D005223:Fats; D005765:Gastrointestinal Agents; C455117:aramchol
keywords: Cholic Acid; Clinical Trial; Lipid; NASH; Steatosis