Clinical Trial: Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients
Brief Summary: Lipodystrophies are rare disorders characterized by selective loss of adipose tissue and predisposition to insulin resistance and its metabolic complications. Hepatic steatosis is a common complication in patients with partial and generalized lipodystrophies.Despite aggressive management of diabetes and hyperlipidemia, hepatic steatosis and its complications present a therapeutic challenge in many patients. Due to this large disease burden, it is important to assess the efficacy and safety of novel therapies for hepatic steatosis in patients with lipodystrophies.There are, however, no systematic studies evaluating various therapeutic interventions for reducing hepatic steatosis in patients with lipodystrophies. A variety of drugs have been investigated in nonlipodystrophic patients with non-alcoholic hepatic steatosis and steatohepatitis (NASH) or non-alcoholic fatty liver disease (NAFLD). Recent data support the activation of the farnesoid X receptor (FXR, NR1H4), a nuclear hormone receptor regulated by bile acids, for treatment of NASH and NAFLD. FXR activates transcription of several genes particularly the atypical nuclear receptor small heterodimer partner (SHP, NR0B2) and thus can influence triglyceride metabolism within hepatocytes.Both cholic acid (CA) and chenodeoxycholic acid (CDCA) are ligands for FXR, however, UDCA which is the 7 hydroxy β-epimer of CDCA, does not activate FXR. Obeticholic acid (OCA) is a first-in-class selective FXR agonist which has approximately 100 fold greater FXR-agonistic activity in the nanomolar range, as compared to CDCA .It therefore appears that FXR modulation offers interesting therapeutic possibilities in treating hepatic steatosis. This study is primarily designed to study efficacy of OCA, a strong FXR ligand, in reducing hepatic triglyceride levels in patients with hepatic steatosis and Familial Partial Lipodystrophy (FPLD). If proven to be effective, it may reduce morbidity and mortality as a result of sequelae of he
Detailed Summary:
This study will be a randomized, placebo-controlled cross-over trial. Patients who are considered eligible for the study will undergo screening evaluation to determine their eligibility for the trial. For those who are found to be eligible, during the baseline period, they will continue their usual diet and other lifestyle measures without changing any medications for 1 month in order to establish a baseline state. Three blood samples will be obtained during this period at the Clinical and Translational Research Center. Following the baseline period, the patients will receive obeticholic acid (OCA) or an identical placebo in the dose of 25 mg/day for a period of 4 months and then will receive the other treatment (OCA or placebo) for 4 months. There will be a wash-out period of 4 months in-between the two study periods.
Patients will be educated to maintain their usual physical activities and diet during the study. The subjects will be admitted to the Clinical and Translational Research Center for the baseline evaluations (at the beginning of the two study periods), and at the end of four months during each study period.
Sponsor: University of Texas Southwestern Medical Center
Current Primary Outcome: Change in the Liver Triglycerides(TG). [ Time Frame: 2 months ]
Original Primary Outcome: Reduction in teh Liver TG [ Time Frame: 2 months ]
Current Secondary Outcome:
Original Secondary Outcome:
Information By: University of Texas Southwestern Medical Center
Dates:
Date Received: April 24, 2015
Date Started: June 2016
Date Completion: September 2018
Last Updated: September 21, 2016
Last Verified: September 2016
