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

Non-alcoholic Steatohepatitis (NASH) Clinical Trial

Official title:

A Randomised Controlled Trial of Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01950884
• Other study ID #: LISTEN
• Secondary ID: 2013-003465-33
• Status: Enrolling by invitation
• Phase: Phase 4
• First received: September 19, 2013
• Last updated: September 23, 2013
• Start date: October 2013
• Est. completion date: December 2014

Study information

• Verified date: September 2013
• Source: University of Palermo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 45
• Est. completion date: December 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1.Patients older 18 years

• 2.Histological diagnosis of possible or definite NASH, according to Kleiner scorw, within 6 months before randomization -

Exclusion Criteria:

• 1)Average alcohol consumption > 20 g per day in women and > 30 g per day in men

• 2)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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Steatohepatitis (NASH)

Intervention

Drug:
• Ezetimibe
Ezetimibe tablets

Behavioral:
• Lifestyle
lifestyle

Locations

Country	Name	City	State
Italy	Dipartimento Biomedico di Medicina Interna e Specialistica Di.Bi.M.I.S.	Palermo

Sponsors (1)

Lead Sponsor	Collaborator
University of Palermo

Country where clinical trial is conducted

Italy, 

References & Publications (16)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2005 Jan 25. — View Citation

Ekstedt M, Franzén 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. — View Citation

Fassio E, Alvarez E, Domínguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004 Oct;40(4):820-6. — View Citation

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. — View Citation

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. Epub 2006 Jul 10. — View Citation

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. Erratum in: Hepatology. 2003 Aug;38(2):536. — View Citation

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. — View Citation

Petta S, Muratore C, Craxì 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in the prevalence and severity of metabolic syndrome and the cardiovascular risk profile (Framingham calculator)		52 weeks	Yes
Primary	HISTOLOGICAL IMPROVEMENT IN THE SEVERITY OF NASH	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; at least 1 point improvement in the score for ballooning degeneration; no worsening of the fibrosis score.	52 WEEKS	Yes
Secondary	Changes in individual components of NAS score	Changes in: steatosis, lobular inflammation and hepatocellular balloonin; fibrosis; serum aminotransferase levels; anthropometric measures, visceral adiposity index (VAI), insulin resistence, lipid profile and liver elastometry.	6 weeks, 24 weeks, 52 weeks	Yes