Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis

NCT01950884 | Unknown Phase 4 DMC

• 2 other identifiers: LISTEN2013-003465-33
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

• NAFLD (Non-alcoholic fatty liver disease) has become the most common cause of liver disease in Western countries (hepatic manifestation of insulin resistance);
• NAFLD represents a cardiovascular risk factor;
• Lifestyle modification(weight loss)is the effective medical treatment recommended for NASH (Non-alcoholic Steatohepatitis);
• Ezetimibe could represent a novel safe treatment for NAFLD (Patel 2006. Here the investigators propose a Randomized Controlled Pilot Trial to evaluate the addictive effect of ezetimibe on liver histology, biochemical and sonographic parameters in a small (n.40) number of NASH patients randomized for 12 months in two arms: lifestyle vs lifestyle+ezetimibe.

Conditions

•Non-alcoholic Steatohepatitis (NASH)

Keywords

•Non-alcoholic Steatohepatitis (NASH)

Outcome Measures

Primary Outcomes (1)

• HISTOLOGICAL IMPROVEMENT IN THE SEVERITY OF NASH

  1. either improvement in NAS by at least 2 points spread across at least 2 of the NAS components or post-treatment NAS of 3 points or less; 2. at least 1 point improvement in the score for ballooning degeneration; 3. no worsening of the fibrosis score.

  52 WEEKS

Secondary Outcomes (1)

• Changes in individual components of NAS score

  6 weeks, 24 weeks, 52 weeks

Other Outcomes (1)

• Changes in the prevalence and severity of metabolic syndrome and the cardiovascular risk profile (Framingham calculator)

  52 weeks

Study Arms (2)

Ezetimibe

EXPERIMENTAL

Ezetimibe tablets plus lifestyle

Drug: Ezetimibe; Behavioral: Lifestyle

lifestyle

ACTIVE COMPARATOR

lifestyle

Behavioral: Lifestyle

Interventions

Ezetimibe DRUG

Ezetimibe tablets

Ezetimibe

Lifestyle BEHAVIORAL

lifestyle

Ezetimibe; lifestyle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older 18 years
• Histological diagnosis of possible or definite NASH, according to Kleiner scorw, within 6 months before randomization -

You may not qualify if:

• )Average alcohol consumption \> 20 g per day in women and \> 30 g per day in men
• )other causes of chronic liver disease 3) History of or planned gastrointestinal bypass or any additional bariatric surgery/intervention 4)Hepatic cirrhosis with Child-Pugh score of B or C, and/or concomitant HCC 5)Recent(within 6 months) or concomitant use of agents known to cause hepatic steatosis 7)Recent(within 6 months)change in dose/regimen or first treatment with vitamin E, C, betaine, s-adenosylmethionine, ursodeoxycholate, sylimarin, fibrate, statin, pentoxyfilline, angiotensin II inhibitors, orlistat, sibutramine 8)Ongoing or recent therapy (within 6 months) with vitamin D or with medications known to affect vitamin D3 metabolism 9)Any additional condition that might interfere with optimal partecipation in the study, according to Investigators opinion; 10)Be pregnant or breastfeeding.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (1)

Dipartimento Biomedico di Medicina Interna e Specialistica Di.Bi.M.I.S.

Palermo, Italy, 90127, Italy

Location

Related Publications (17)

• Hughes EA, Tracey I, Singhal S, Patel J. Unexpected beneficial effect in the use of ezetimibe in non-alcoholic fatty liver disease. Med Hypotheses. 2006;67(6):1463-4. doi: 10.1016/j.mehy.2006.05.041. Epub 2006 Jul 10. No abstract available.

  PMID: 16831521 BACKGROUND

• Petta S, Muratore C, Craxi A. Non-alcoholic fatty liver disease pathogenesis: the present and the future. Dig Liver Dis. 2009 Sep;41(9):615-25. doi: 10.1016/j.dld.2009.01.004. Epub 2009 Feb 14.

  PMID: 19223251 BACKGROUND

• Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003 Apr;37(4):917-23. doi: 10.1053/jhep.2003.50161.

  PMID: 12668987 BACKGROUND

• Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology. 2005 Jul;42(1):44-52. doi: 10.1002/hep.20734.

  PMID: 15895401 BACKGROUND

• Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006 Oct;44(4):865-73. doi: 10.1002/hep.21327.

  PMID: 17006923 BACKGROUND

• Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004 Oct;40(4):820-6. doi: 10.1002/hep.20410.

  PMID: 15382171 BACKGROUND

• Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005 Jul;129(1):113-21. doi: 10.1053/j.gastro.2005.04.014.

  PMID: 16012941 BACKGROUND

• Targher G, Marra F, Marchesini G. Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon? Diabetologia. 2008 Nov;51(11):1947-53. doi: 10.1007/s00125-008-1135-4. Epub 2008 Sep 2.

  PMID: 18762907 BACKGROUND

• Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, Fava JL, Wing RR. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010 Jan;51(1):121-9. doi: 10.1002/hep.23276.

  PMID: 19827166 BACKGROUND

• Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, Powell EE. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut. 2004 Mar;53(3):413-9. doi: 10.1136/gut.2003.027581.

  PMID: 14960526 BACKGROUND

• Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR; NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010 May 6;362(18):1675-85. doi: 10.1056/NEJMoa0907929. Epub 2010 Apr 28.

  PMID: 20427778 BACKGROUND

• Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006 Nov 30;355(22):2297-307. doi: 10.1056/NEJMoa060326.

  PMID: 17135584 BACKGROUND

• Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology. 2010 Jul;52(1):79-104. doi: 10.1002/hep.23623.

  PMID: 20578268 BACKGROUND

• Subramanian S, Goodspeed L, Wang S, Kim J, Zeng L, Ioannou GN, Haigh WG, Yeh MM, Kowdley KV, O'Brien KD, Pennathur S, Chait A. Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice. J Lipid Res. 2011 Sep;52(9):1626-35. doi: 10.1194/jlr.M016246. Epub 2011 Jun 20.

  PMID: 21690266 BACKGROUND

• Davies JP, Scott C, Oishi K, Liapis A, Ioannou YA. Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia. J Biol Chem. 2005 Apr 1;280(13):12710-20. doi: 10.1074/jbc.M409110200. Epub 2005 Jan 25.

  PMID: 15671032 BACKGROUND

• Chan DC, Watts GF, Gan SK, Ooi EM, Barrett PH. Effect of ezetimibe on hepatic fat, inflammatory markers, and apolipoprotein B-100 kinetics in insulin-resistant obese subjects on a weight loss diet. Diabetes Care. 2010 May;33(5):1134-9. doi: 10.2337/dc09-1765. Epub 2010 Feb 25.

  PMID: 20185740 BACKGROUND

• Noto D, Petta S, Giammanco A, Spina R, Cabibbi D, Porcasi R, Caldarella R, Ciaccio M, Muratore R, Cefalu AB, Craxi A, Averna M. Lifestyle versus ezetimibe plus lifestyle in patients with biopsy-proven non-alcoholic steatohepatitis (LISTEN): A double-blind randomised placebo-controlled trial. Nutr Metab Cardiovasc Dis. 2022 May;32(5):1288-1291. doi: 10.1016/j.numecd.2022.01.024. Epub 2022 Jan 29.

  PMID: 35256232 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Maurizio Averna, Professor

  University of Palermo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: September 26, 2013
• Study Start: October 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: December 1, 2014
• Last Updated: September 26, 2013

Record last verified: 2013-09

Locations

IT (1)