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The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease.
Clin Gastroenterol Hepatol 2014; 12(12):2085-91.e1CG

Abstract

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 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+Show Affiliations

Liver and Gastroenterology Unit, Division of Medicine, Hadassah University Medical Center, Jerusalem, Israel; Holy Family Hospital, Nazareth, Israel. Electronic address: safadi@hadassah.org.il.Department of Gastroenterology and Hepatology, University of Tel Aviv, Meir Medical Center, Kfar Saba, Israel.Holy Family Hospital, Nazareth, Israel.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.Galmed Medical Research, Limited, Tel-Aviv, Israel.Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel; Galmed Medical Research, Limited, Tel-Aviv, Israel.Liver and Gastroenterology Unit, Division of Medicine, Hadassah University Medical Center, Jerusalem, Israel; Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel.No affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24815326

Citation

Safadi, Rifaat, et al. "The Fatty Acid-bile Acid Conjugate Aramchol Reduces Liver Fat Content in Patients With Nonalcoholic Fatty Liver Disease." Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, vol. 12, no. 12, 2014, pp. 2085-91.e1.
Safadi R, Konikoff FM, Mahamid M, et al. The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014;12(12):2085-91.e1.
Safadi, R., Konikoff, F. M., Mahamid, M., Zelber-Sagi, S., Halpern, M., Gilat, T., & Oren, R. (2014). The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, 12(12), pp. 2085-91.e1. doi:10.1016/j.cgh.2014.04.038.
Safadi R, et al. The Fatty Acid-bile Acid Conjugate Aramchol Reduces Liver Fat Content in Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2014;12(12):2085-91.e1. PubMed PMID: 24815326.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. AU - Safadi,Rifaat, AU - Konikoff,Fred M, AU - Mahamid,Mahmud, AU - Zelber-Sagi,Shira, AU - Halpern,Maya, AU - Gilat,Tuvia, AU - Oren,Ran, AU - ,, Y1 - 2014/05/09/ PY - 2013/12/18/received PY - 2014/04/09/revised PY - 2014/04/14/accepted PY - 2014/5/13/entrez PY - 2014/5/13/pubmed PY - 2015/7/25/medline KW - Cholic Acid KW - Clinical Trial KW - Lipid KW - NASH KW - Steatosis SP - 2085 EP - 91.e1 JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JO - Clin. Gastroenterol. Hepatol. VL - 12 IS - 12 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 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. SN - 1542-7714 UR - https://www.unboundmedicine.com/medline/citation/24815326/The_fatty_acid_bile_acid_conjugate_Aramchol_reduces_liver_fat_content_in_patients_with_nonalcoholic_fatty_liver_disease_ DB - PRIME DP - Unbound Medicine ER -