Back to resultsLifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis
Primary Purpose
•Non-alcoholic Steatohepatitis (NASH)
Status
Unknown status
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
Ezetimibe
Lifestyle
Sponsored by
About this trial
This is an interventional treatment trial for •Non-alcoholic Steatohepatitis (NASH) focused on measuring •Non-alcoholic Steatohepatitis (NASH)
Eligibility Criteria
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.
Sites / Locations
- Dipartimento Biomedico di Medicina Interna e Specialistica Di.Bi.M.I.S.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ezetimibe
lifestyle
Arm Description
Ezetimibe tablets plus lifestyle
lifestyle
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT01950884
First Posted
September 19, 2013
Last Updated
September 23, 2013
Sponsor
University of Palermo
1. Study Identification
Unique Protocol Identification Number
NCT01950884
Brief Title
Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis
Official Title
A Randomised Controlled Trial of Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2013
Overall Recruitment Status
Unknown status
Study Start Date
October 2013 (undefined)
Primary Completion Date
October 2014 (Anticipated)
Study Completion Date
December 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Palermo
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
•Non-alcoholic Steatohepatitis (NASH)
Keywords
•Non-alcoholic Steatohepatitis (NASH)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ezetimibe
Arm Type
Experimental
Arm Description
Ezetimibe tablets plus lifestyle
Arm Title
lifestyle
Arm Type
Active Comparator
Arm Description
lifestyle
Intervention Type
Drug
Intervention Name(s)
Ezetimibe
Intervention Description
Ezetimibe tablets
Intervention Type
Behavioral
Intervention Name(s)
Lifestyle
Intervention Description
lifestyle
Primary Outcome Measure Information:
Title
HISTOLOGICAL IMPROVEMENT IN THE SEVERITY OF NASH
Description
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.
Time Frame
52 WEEKS
Secondary Outcome Measure Information:
Title
Changes in individual components of NAS score
Description
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.
Time Frame
6 weeks, 24 weeks, 52 weeks
Other Pre-specified Outcome Measures:
Title
Changes in the prevalence and severity of metabolic syndrome and the cardiovascular risk profile (Framingham calculator)
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maurizio Averna, Professor
Organizational Affiliation
University of Palermo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dipartimento Biomedico di Medicina Interna e Specialistica Di.Bi.M.I.S.
City
Palermo
ZIP/Postal Code
90127
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
16831521
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. doi: 10.1016/j.mehy.2006.05.041. Epub 2006 Jul 10. No abstract available.
Results Reference
background
PubMed Identifier
19223251
Citation
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.
Results Reference
background
PubMed Identifier
12668987
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. doi: 10.1053/jhep.2003.50161. Erratum In: Hepatology. 2003 Aug;38(2):536.
Results Reference
background
PubMed Identifier
15895401
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. doi: 10.1002/hep.20734.
Results Reference
background
PubMed Identifier
17006923
Citation
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.
Results Reference
background
PubMed Identifier
15382171
Citation
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.
Results Reference
background
PubMed Identifier
16012941
Citation
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.
Results Reference
background
PubMed Identifier
18762907
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.
Results Reference
background
PubMed Identifier
19827166
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.
Results Reference
background
PubMed Identifier
14960526
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. doi: 10.1136/gut.2003.027581.
Results Reference
background
PubMed Identifier
20427778
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.
Results Reference
background
PubMed Identifier
17135584
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. doi: 10.1056/NEJMoa060326.
Results Reference
background
PubMed Identifier
20578268
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.
Results Reference
background
PubMed Identifier
21690266
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.
Results Reference
background
PubMed Identifier
15671032
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. doi: 10.1074/jbc.M409110200. Epub 2005 Jan 25.
Results Reference
background
PubMed Identifier
20185740
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.
Results Reference
background
PubMed Identifier
35256232
Citation
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.
Results Reference
derived
Learn more about this trial
Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis
We'll reach out to this number within 24 hrs