TY - JOUR
T1 - The Fatty Acid-Bile Acid Conjugate Aramchol Reduces Liver Fat Content in Patients With Nonalcoholic Fatty Liver Disease
AU - the FLORA Group
AU - Safadi, Rifaat
AU - Konikoff, Fred M.
AU - Mahamid, Mahmud
AU - Zelber-Sagi, Shira
AU - Halpern, Maya
AU - Gilat, Tuvia
AU - Oren, Ran
N1 - Publisher Copyright:
© 2014 AGA Institute.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Background & Aims: 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 300mg/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.
AB - Background & Aims: 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 300mg/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.
KW - Cholic Acid
KW - Clinical Trial
KW - Lipid
KW - NASH
KW - Steatosis
UR - http://www.scopus.com/inward/record.url?scp=84918843434&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2014.04.038
DO - 10.1016/j.cgh.2014.04.038
M3 - Article
C2 - 24815326
AN - SCOPUS:84918843434
SN - 1542-3565
VL - 12
SP - 2085-2091.e1
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 12
ER -