Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients
Status:
Recruiting
Trial end date:
2022-01-01
Target enrollment:
Participant gender:
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.