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Cholic Acid for Hepatic Steatosis in Lipodystrophy

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified August 2011 by University of Texas Southwestern Medical Center.
Recruitment status was:  Active, not recruiting
FDA Office of Orphan Products Development
Information provided by:
University of Texas Southwestern Medical Center Identifier:
First received: April 4, 2007
Last updated: August 2, 2011
Last verified: August 2011
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.

Condition Intervention Phase
Hepatic Steatosis
Drug: Cholic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Study of Cholic Acid for Hepatic Steatosis in Lipodystrophy Patients

Resource links provided by NLM:

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Reduction in liver triglyceride content as measured by liver MRS. [ Time Frame: Month 3, 6, 9 and 12 ]

Secondary Outcome Measures:
  • Reduction in serum triglycerides, ALT, AST and GGT. [ Time Frame: Month 3,6,9 and 12 ]

Estimated Enrollment: 20
Study Start Date: April 2006
Estimated Study Completion Date: October 2013
Estimated Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cholic Acid active capsules
Cholic Acid weight based dose for 6 months double-blind
Drug: 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
Placebo for Cholic Acid for 6 months double-blind
Drug: 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.

Detailed 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.

Ages Eligible for Study:   6 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00457639

United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-9052
Sponsors and Collaborators
University of Texas Southwestern Medical Center
FDA Office of Orphan Products Development
Principal Investigator: Abhimanyu Garg, M.D. University of Texas Southwestern Medical Center
  More Information

Responsible Party: Dr Abhimanyu Garg, UT Southwestern Medical Center Identifier: NCT00457639     History of Changes
Other Study ID Numbers: 3085
Study First Received: April 4, 2007
Last Updated: August 2, 2011

Keywords provided by University of Texas Southwestern Medical Center:

Additional relevant MeSH terms:
Fatty Liver
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Liver Diseases
Digestive System Diseases
Cholic Acids
Gastrointestinal Agents processed this record on May 25, 2017