NCT02430077

Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients

Completed Phase 2 Results posted Last updated 22 August 2024

What this trial tests

Phase 2 trial testing Obeticholic Acid in Familial Partial Lipodystrophy in 10 participants. Completed in 1 December 2022.

Timeline

1 June 2016

Primary endpoint
1 October 2022

1 December 2022

Quick facts

Lead sponsor	Abhimanyu Garg
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	10
Start date	1 June 2016
Primary completion	1 October 2022
Estimated completion	1 December 2022
Sites	2 locations across United States

Drugs / interventions tested

• Obeticholic Acid (OBETICHOLIC ACID) — full drug profile →
• Placebo

Conditions studied

• Familial Partial Lipodystrophy — all drugs for Familial Partial Lipodystrophy →

Sponsor

Abhimanyu Garg

Who can join

Adults 18 to 70, any sex, with Familial Partial Lipodystrophy. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Change in the Liver Triglycerides (TG).
  Time frame: Baseline, 4 months
  The primary end-point variable was the change in the liver TG content assessed using proton-density fat fraction mapping by Magnetic Resonance Imaging (MRI).

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases.
   Guan B, Tong J, Hao H, Yang Z, et al · · 2022 · cited 142× · PMID 35646540 · DOI 10.1016/j.apsb.2021.12.011
2. Update on FXR Biology: Promising Therapeutic Target?
   Han CY. · · 2018 · cited 133× · PMID 30013008 · DOI 10.3390/ijms19072069
3. Review article: therapeutic aspects of bile acid signalling in the gut-liver axis.
   Simbrunner B, Trauner M, Reiberger T. · · 2021 · cited 63× · PMID 34555862 · DOI 10.1111/apt.16602
4. Farnesoid X Receptor Agonists as Therapeutic Target for Cardiometabolic Diseases.
   Li C, Yang J, Wang Y, Qi Y, et al · · 2020 · cited 32× · PMID 32982723 · DOI 10.3389/fphar.2020.01247
5. Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.
   Jin P, Duan X, Huang Z, Dong Y, et al · · 2025 · cited 21× · PMID 40717128 · DOI 10.1038/s41392-025-02270-3
6. Role of bile acids in overweight and obese children and adolescents.
   Giannini C, Mastromauro C, Scapaticci S, Gentile C, et al · · 2022 · cited 18× · PMID 36531484 · DOI 10.3389/fendo.2022.1011994
7. Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).
   Sun Y, Sun K, Ling H, Xia Q. · · 2025 · cited 2× · PMID 40376981 · DOI 10.3892/ijmm.2025.5551
8. Efficacy and Safety of Obeticholic Acid for Treating Hepatic Steatosis in Patients With Familial Partial Lipodystrophy.
   Garg A, Vasandani C, Li X, Quittner C, et al · · 2025 · cited 2× · PMID 40080694 · DOI 10.1210/clinem/dgaf173