This trial is active, not recruiting.

Condition hepatic steatosis
Treatment cholic acid
Phase phase 2
Sponsor University of Texas Southwestern Medical Center
Collaborator FDA Office of Orphan Products Development
Start date April 2006
End date October 2011
Trial size 20 participants
Trial identifier NCT00457639, 3085, FD003085


To evaluate the efficacy and safety of cholic acid therapy in treating lipodystrophy patients with hepatic steatosis. This is a randomized, double-blind, placebo-controlled cross-over study.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Cholic Acid weight based dose for 6 months double-blind
cholic acid
Capsules of active Cholic Acid or matching placebo, total dose is 15 mg/kg per day, maximum dose of 1500 mg per day, taken PO, BID.
(Placebo Comparator)
Placebo for Cholic Acid for 6 months double-blind
cholic acid
Capsules of active Cholic Acid or matching placebo, total dose is 15 mg/kg per day, maximum dose of 1500 mg per day, taken PO, BID.

Primary Outcomes

Reduction in liver triglyceride content as measured by liver MRS.
time frame: Month 3, 6, 9 and 12

Secondary Outcomes

Reduction in serum triglycerides, ALT, AST and GGT.
time frame: Month 3,6,9 and 12

Eligibility Criteria

Male or female participants from 6 years up to 70 years old.

Inclusion Criteria: - Patients with lipodystrophies as diagnosed by clinical criteria. - Hepatic steatosis (>5.6% hepatic triglyceride content) as demonstrated by 1H magnetic resonance spectroscopy. - Age 6-70 years. - Alcohol intake of less than 40 g per week. Exclusion Criteria: - Laboratory or other histologic findings highly suggestive of liver disease due to causes other than non-alcoholic steatohepatitis, such as chronic viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, biliary obstruction or genetic liver diseases such as Wilson's disease, hemochromatosis or alpha-1-antitrypsin deficiency. - Treatment with drugs associated with steatohepatitis, e.g., corticosteroids, high dose estrogens, methotrexate, amiodarone, , sulfasalazine, or oxacillin in the 6 months prior to the study. - Decompensated liver disease as evidenced by clinical features of hepatic failure (variceal bleeding, ascites, hepatic encephalopathy etc.) and laboratory investigations (prolonged prothrombin time, hypoalbuminemia, presence of esophageal varices etc.) - Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study suggestive of liver cancer. - Use of drugs which can potentially decrease hepatic steatosis during previous 3 months; ursodeoxycholic acid, high-dose vitamin E, betaine, acetylcysteine and choline. Thiazolidinediones are allowed if dose has been stable for 3 months prior to screening. - Significant systemic or major illnesses other than liver disease, such as congestive heart failure, cerebrovascular disease, respiratory failure, renal failure (serum creatinine >2 mg/dL), acute pancreatitis, organ transplantation, serious psychiatric disease, and malignancy, that could interfere with the trial and adequate follow up. - Acute medical illnesses precluding participation in the studies. - Known HIV-infected patient. - Current substance abuse. - Pregnant or lactating women. - Hematocrit of less than 30%. - History of weight loss during past 3 months. - Patients on bile acid binding resins, cholestyramine, colestipol, colesevelam. - Hypersensitivity or intolerance to CA or any components of its formulation

Additional Information

Official title Phase II Study of Cholic Acid for Hepatic Steatosis in Lipodystrophy Patients
Principal investigator Abhimanyu Garg, M.D.
Description Lipodystrophies are rare disorders characterized by selective loss of adipose tissue and predisposition to develop insulin resistance and its associated metabolic complications such as dyslipidemia, diabetes mellitus and hepatic steatosis. Nonalcoholic hepatic steatosis or steatohepatitis caused by excessive accumulation of triglycerides in hepatocytes, in fact, is a common feature of these disorders. Often a cause for significant morbidity and even mortality in lipodystrophic patients, hepatic steatosis poses a significant therapeutic challenge. Recent insight into the role of primary bile acids, cholic acid and chenodeoxycholic acid, which are endogenous ligands for the farnesoid X receptor (FXR), in regulating hepatic triglyceride homeostasis offers new treatment options for hepatic steatosis. Cholic acid was shown to inhibit hepatic triglyceride accumulation by more than 50% in a mouse model of hepatic steatosis and hypertriglyceridemia. Cholic acid has been previously used to treat inborn errors of bile acid synthesis in children without any side effects. In other studies in adults, cholic acid has been reported to be well tolerated. Therefore, we propose to investigate a potentially safe therapeutic option for its efficacy in reducing hepatic steatosis in patients with lipodystrophies.
Trial information was received from ClinicalTrials.gov and was last updated in August 2011.
Information provided to ClinicalTrials.gov by University of Texas Southwestern Medical Center.