Weight Management in Nonalcoholic Steatohepatitis

• ClinicalTrials.gov Identifier: NCT00266019
• Recruitment Status: Completed
• First Posted: December 15, 2005
• Last Update Posted: January 13, 2010
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Tracking Information

• First Submitted Date: December 14, 2005
• First Posted Date: December 15, 2005
• Last Update Posted Date: January 13, 2010
• Study Start Date: January 2005
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: March 13, 2007)

• Liver histology score (NASH-Clinical Research Network [CRN] scoring system) at 48 weeks
• Weight reduction at 48 weeks

Original Primary Outcome Measures (submitted: December 14, 2005)

• Liver Histology Score (NASH-CRN scoring system) at 48 weeks
• Weight reduction at 48 weeks

Current Secondary Outcome Measures (submitted: December 14, 2005)

• Insulin sensitivity at 48 weeks
• Liver function test at 48 weeks
• Inflammatory markers and adipokine levels at 48 weeks
• Quality of life at 48 weeks

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Weight Management in Nonalcoholic Steatohepatitis
• Official Title: Weight Management in Nonalcoholic Steatohepatitis (NASH)
• Brief Summary: Nonalcoholic steatohepatitis (NASH) is one of the most common chronic liver diseases. The cause of NASH is not completely understood and currently there is no effective treatment for this disease. An effective approach to treatment is needed since without treatment this disease may progress to fibrosis and cirrhosis. Obesity is one of the most important risk factors for NASH and weight reduction is generally recommended as an initial step in its management. However, there are very limited data on the efficacy of weight reduction as a treatment for NASH. Data from uncontrolled trials using poorly defined primary outcome measures and patient populations and nonstandardized weight loss interventions suggest that modest weight loss may improve fatty liver disease. The objective of this project is to conduct a randomized controlled trial of weight reduction in the management of NASH using a combination of diet, exercise, and behavior modification.
• Detailed Description: Nonalcoholic steatohepatitis (NASH) is one of the most common chronic liver diseases. The cause of NASH is not completely understood and currently there is no effective treatment for this disease. An effective approach to treatment is needed since without treatment this disease may progress to fibrosis and cirrhosis. Obesity is one of the most important risk factors for NASH and weight reduction is generally recommended as an initial step in its management. However, there has never been a randomized controlled trial evaluating the efficacy of weight reduction as a treatment for NASH. Data from uncontrolled trials using poorly defined primary outcome measures and patient populations and nonstandardized weight loss interventions suggest that modest weight loss may improve liver histology. The objective of this project is to conduct a pilot study in preparation for a randomized controlled trial of weight reduction in the management of NASH. In this study, 30 overweight or obese individuals with biopsy-proven NASH will be enrolled. Twenty patients will be randomized to receive 48 weeks of intensive weight management using a combination of diet, exercise and behavior modification with a goal of 7-10% weight reduction. This weight loss program is similar to programs used successfully in other overweight populations and to the intensive lifestyle program of the Diabetes Prevention Program and Look AHEAD. The other 10 patients will be randomized to a control group where they will receive standard medical care and general counseling on healthy eating and exercise. At the end of the 48-week study, patients will have a repeat liver biopsy that will be compared to their baseline biopsy. The pilot study will establish the feasibility of recruiting and retaining, producing sustained weight loss and performing repeat liver biopsies in this population. Based on the outcomes of this preliminary trial, this program will be further refined and readied for a larger-scale clinical trial.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Fatty Liver
• Intervention: Behavioral: Weight Management (diet, exercise, and behavior modification)
• Study Arms: Not Provided

Publications *

• Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393-403.
• Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980 Jul;55(7):434-8.
• Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology. 1994 Oct;107(4):1103-9.
• Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21.
• Ueno T, Sugawara H, Sujaku K, Hashimoto O, Tsuji R, Tamaki S, Torimura T, Inuzuka S, Sata M, Tanikawa K. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol. 1997 Jul;27(1):103-7.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: December 14, 2005): 30
• Original Enrollment: Same as current
• Actual Study Completion Date: December 2007
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

1. Evidence of chronic steatohepatitis on liver biopsy.
2. Elevated alanine or aspartate aminotransferase values (ALT > 41 or AST > 34) within 3 months of enrollment
3. Absence of another form of liver disease
4. Body mass index between 25-50 kg/m2.
5. At least 18 years of age
6. Absence of significant alcohol consumption (more than one standard drink per day).
7. Able to walk 2 blocks or a quarter of a mile without stopping
8. Willing to complete a two-week run-in period with successful completion of self-monitoring records.

Exclusion Criteria:

1. < 18 years of age
2. Significant alcohol consumption (> 1 standard drink per day)
3. Contraindications to obtaining a liver biopsy
4. Unable to walk 2 blocks or a quarter of a mile without stopping
5. Currently pregnant or pregnant in the previous six months
6. Currently engaged in an active weight-loss program or taking weight-loss medication
7. Report conditions that, in the judgment of the investigators, render potential participants unlikely to follow the protocol for 12 months, including illness likely to be terminal within 2 years, plans to move, substance abuse, or other significant psychiatric problems

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00266019
• Other Study ID Numbers: DK67363 (completed)
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kittichai Promrat, M.D.; Rhode Island Hospital/Brown University

• PRS Account: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Verification Date: January 2010