Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients
Condition: Familial Partial Lipodystrophy
MeSH terms: Lipodystrophy, Familial Partial; Lipodystrophy
Study type: Interventional
Phase: Phase 2

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 hepatic steatosis in patients with lipodystrophies.
    

Detailed description: 
      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.
    

Intervention name(s): Obeticholic Acid; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Capsules of obeticholic acid (OCA) or an identical placebo in the dose of 25 mg/day for a period of 4 months .; Identical to Obeticholic Acid - placebo drug
Other intervention name(s): NEW DRUG APPLICATION; Identical to Obeticholic Acid placebo drug
Intervention MeSH terms: Chenodeoxycholic Acid
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Hepatic Steatosis