Clinical trial NCT00457938: Novel Therapies for Metabolic Complications of Lipodystrophies
Official title: Novel Therapies for Metabolic Complications in Patients With Lipodystrophies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Resistance
Hypertriglyceridemia
Diabetes
Hepatic Steatosis
Keywords: lipodystrophy
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Takeda
name: Amylin Pharmaceuticals, LLC.
First posted: 2007-04-09
Enrollment: 4
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Lipodystrophies represent a therapeutic challenge with regards to the management of the diabetes, insulin resistance, hypertriglyceridemia and fatty liver which frequently present in conjunction with significant adipose tissue loss. The purpose of the study and it's four subprojects is to examine the safety and efficacy of various novel interventions designed to improve or resolve the fatty liver, hypertriglyceridemia, and insulin resistance or diabetes that is seen in these patients.

Detailed description: We propose novel therapeutic approaches for the management of metabolic complications in patients with lipodystrophies. The four interventions to be tested are:

Hypothesis 1: An extremely low fat diet.

Eligibility criteria: Inclusion Criteria:

General Inclusion criteria:

* Patients with lipodystrophies as diagnosed by clinical criteria
* Any one of the following:

  * Diabetes mellitus, or
  * Fasting serum triglycerides greater than 200 mg/dL, or
  * Fasting serum insulin greater than 30 U/mL, or
  * Hepatic steatosis ( greater than 5.6% hepatic triglyceride content) as demonstrated by 1H MRS.

Exclusion Criteria:

* Known liver disease due to causes other than non-alcoholic steatohepatitis:
* Current alcohol abuse (more than 7 drinks or 210 g per wk for women and more than 14 drinks or 420 g per wk for men).
* Positive serological markers of hepatitis B and C.
* Autoimmune hepatitis, autoimmune cholestatic liver disorders, Wilson disease and Alpha-1-antitrypsin deficiency as indicated by clinical and laboratory tests.
* Drug-induced liver disease
* Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study suggestive of liver cancer.
* Decompensated liver disease as evidenced by clinical features of hepatic failure (variceal bleeding, ascites, hepatic encephalopathy etc.) and laboratory investigations (prolonged prothrombin time, hypoalbuminemia, presence of esophageal varices etc.)
* Use of the drugs which can potentially decrease hepatic steatosis during previous 3 months; high-dose vitamin E, betaine, acetylcysteine, choline and probucol.
* Significant systemic or major illnesses other than liver disease (congestive heart failure, unstable angina, cerebrovascular disease, respiratory failure, renal failure \[serum creatinine more then 2 mg/dL\], acute pancreatitis, organ transplantation, serious psychiatric disease, and malignancy) that could interfere with the trial and adequate follow up.
* Acute medical illnesses precluding participation in the studies.
* Known HIV infected patient.
* Current substance abuse.
* Pregnant or lactating women.
* Hematocrit of less than 30%.
* History of weight loss ( more than 10%) or use of weight loss drugs such as sibutramine or orlistat in the last 3 months.

Each subproject has additional specific inclusion and exclusion criteria

Primary outcomes:
measure: Project specific: improvement in serum triglycerides, insulin resistance, liver triglyceride content, liver volume, Hgb A1c,
timeFrame: 6 to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Abhimanyu Garg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Simha V, Subramanyam L, Szczepaniak L, Quittner C, Adams-Huet B, Snell P, Garg A. Comparison of efficacy and safety of leptin replacement therapy in moderately and severely hypoleptinemic patients with familial partial lipodystrophy of the Dunnigan variety. J Clin Endocrinol Metab. 2012 Mar;97(3):785-92. doi: 10.1210/jc.2011-2229. Epub 2011 Dec 14.