Back to resultsCholic Acid for Hepatic Steatosis in Lipodystrophy
Primary Purpose
Hepatic Steatosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cholic Acid
Sponsored by
About this trial
This is an interventional treatment trial for Hepatic Steatosis focused on measuring lipodystrophy
Eligibility Criteria
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
Sites / Locations
- University of Texas Southwestern Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Cholic Acid active capsules
Placebo for Cholic Acid
Arm Description
Cholic Acid weight based dose for 6 months double-blind
Placebo for Cholic Acid for 6 months double-blind
Outcomes
Primary Outcome Measures
Hepatic Triglyceride (%)
Measured by proton magnetic resonance spectroscopy (MRS)
Secondary Outcome Measures
Serum Triglycerides
Full Information
NCT ID
NCT00457639
First Posted
April 4, 2007
Last Updated
January 16, 2019
Sponsor
University of Texas Southwestern Medical Center
Collaborators
FDA Office of Orphan Products Development
1. Study Identification
Unique Protocol Identification Number
NCT00457639
Brief Title
Cholic Acid for Hepatic Steatosis in Lipodystrophy
Official Title
Phase II Study of Cholic Acid for Hepatic Steatosis in Lipodystrophy Patients
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
FDA Office of Orphan Products Development
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Steatosis
Keywords
lipodystrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cholic Acid active capsules
Arm Type
Experimental
Arm Description
Cholic Acid weight based dose for 6 months double-blind
Arm Title
Placebo for Cholic Acid
Arm Type
Placebo Comparator
Arm Description
Placebo for Cholic Acid for 6 months double-blind
Intervention Type
Drug
Intervention Name(s)
Cholic Acid
Intervention Description
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 Outcome Measure Information:
Title
Hepatic Triglyceride (%)
Description
Measured by proton magnetic resonance spectroscopy (MRS)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Serum Triglycerides
Time Frame
Months 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Abhimanyu Garg, M.D.
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9052
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23447519
Citation
Ahmad Z, Subramanyam L, Szczepaniak L, Simha V, Adams-Huet B, Garg A. Cholic acid for hepatic steatosis in patients with lipodystrophy: a randomized, controlled trial. Eur J Endocrinol. 2013 Apr 15;168(5):771-8. doi: 10.1530/EJE-12-0969. Print 2013 May.
Results Reference
result
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Cholic Acid for Hepatic Steatosis in Lipodystrophy
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