Protocol Number: 03-DK-0212

Title:

Long-Term Treatment of Nonalcoholic Steatohepatitis With Pioglitazone

Number:

03-DK-0212

Summary:

Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging.

In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH.

Sponsoring Institute:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Insulin Resistance

Obesity

Fatty Liver

Cirrhosis

Diabetes

Pioglitazone

Thiazolidinediones

Peroxisome Proliferator-Advanced Receptor Gamma

PPAR Gama

Nonalcoholic Steatohepatitis

Recruitment Keyword(s):

Hepatitis

Non-Alcoholic Steatohepatitis

NASH

Fatty Liver

Condition(s):

Hepatitis

Investigational Drug(s):

Actos (Pioglitazone)

Investigational Device(s):

None

Interventions:

Drug: Actos (Pioglitazone)

Supporting Site:

National Institute of Diabetes and Digestive and Kidney Diseases

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Byron D, Clinical hepatology: profile of an urban, hospital-based practice. Hepatology. 1996 Oct;24(4):813-5.

Ludwig J, Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980 Jul;55(7):434-8.

Caldwell SH, Cryptogenic cirrhosis: clinical characterization andrisk factors for underlying disease. Hepatology. 1999Mar;29(3):664-9.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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