Phase 2 Study of Obeticholic Acid for Lipodystrophy Patients



Status:Recruiting
Conditions:Endocrine
Therapuetic Areas:Endocrinology
Healthy:No
Age Range:18 - 70
Updated:10/17/2018
Start Date:June 2016
End Date:December 2019
Contact:Claudia Quittner, RN
Email:claudia.quittner@utsouthwestern.edu
Phone:214-648-9296

Use our guide to learn which trials are right for you!

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.

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.

Inclusion Criteria:

1. Patients with familial partial lipodystrophy of the Dunnigan variety with heterozygous
disease-causing missense mutation in lamin A/C (LMNA) gene.

2. Hepatic steatosis (>5.6% hepatic triglyceride content) as demonstrated by 1H magnetic
resonance spectroscopy.

3. Age 18-70 years.

4. Alcohol intake of less than 20 g per day in females and 30 g per day in males.

5. Participants and their partners with whom they are having sex, must use
medically-acceptable birth control (contraceptives) during the study.
Medically-acceptable methods of contraception include: (1) surgical sterilization,
such as hysterectomy, tubal ligation or vasectomy. (2) approved hormonal
contraceptives, such as birth control pills, patch or ring; Depo-Provera, Implanon.
(3) barrier methods, such as condom, cervical cap or diaphragm used with a spermicide.
(4) an intrauterine device (IUD).

Exclusion Criteria:

1. 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.

2. Treatment with drugs associated with steatohepatitis, e.g., corticosteroids, high dose
estrogens, methotrexate, amiodarone, tamoxifen, valproic acid, sulfasalazine, or
oxacillin for more than 2 weeks in the 6 months prior to the study.

3. Decompensated liver disease as evidenced by clinical features of hepatic failure
(variceal bleeding, ascites, hepatic encephalopathy etc.) and laboratory
investigations (prolonged prothrombin time with INR > 1.3, hypoalbuminemia with serum
albumin less than 3.0 g/dL, direct bilirubin > 1.3 mg/dL, or presence of esophageal
varices etc.)

4. Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml
and/or liver mass on imaging study suggestive of liver cancer.

5. Use of drugs which can potentially decrease hepatic steatosis during previous 3
months; ursodeoxycholic acid, thiazolidinediones, high-dose vitamin E, betaine,
acetylcysteine and choline.

6. 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.

7. Acute medical illnesses precluding participation in the studies.

8. Known HIV-infected patient.

9. Current substance abuse.

10. Pregnant or lactating woman.

11. Hematocrit of less than 30%.

12. History of weight loss during past 3 months.

13. Patients on bile acid binding resins, cholestyramine, colestipol or colesevelam.

14. Hypersensitivity or intolerance to OCA or any components of its formulation.

15. Failure to give informed consent 16 .Previous clinical diagnosis of diabetes mellitus
or fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%.
We found this trial at
2
sites
Dallas, Texas 75390
Principal Investigator: Abhimanyu Garg, MD
?
mi
from
Dallas, TX
Click here to add this to my saved trials
2201 Inwood Rd
Dallas, Texas 75235
(214) 645-8300
Phone: 214-648-9296
U.T. Southwestern Medical Center The story of UT Southwestern Medical Center is one of commitment...
?
mi
from
Dallas, TX
Click here to add this to my saved trials