Novel Therapies for Metabolic Complications of Lipodystrophies

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of Texas Southwestern Medical Center
Sponsor:
Collaborators:
Takeda
Amylin Pharmaceuticals, LLC.
Information provided by (Responsible Party):
Abhimanyu Garg, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00457938
First received: April 4, 2007
Last updated: June 19, 2013
Last verified: June 2013

April 4, 2007
June 19, 2013
April 2006
August 2016   (final data collection date for primary outcome measure)
Project specific: improvement in serum triglycerides, insulin resistance, liver triglyceride content, liver volume, Hgb A1c, [ Time Frame: 6 to 12 months ] [ Designated as safety issue: No ]
Project specific: improvement in serum triglycerides, insulin resistance, liver triglyceride content, liver volume, Hgb A1c,
Complete list of historical versions of study NCT00457938 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Novel Therapies for Metabolic Complications of Lipodystrophies
Novel Therapies for Metabolic Complications in Patients With Lipodystrophies

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.

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. Hypothesis 2: Leptin replacement therapy. Hypothesis 3: Cholic acid therapy.. Hypothesis 4: Peroxisome proliferator activated receptors (PPAR) agonist, pioglitazone.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Insulin Resistance
  • Hypertriglyceridemia
  • Diabetes
  • Hepatic Steatosis
  • Other: low-fat diet ( Still recruiting )
    This study will compare 10% fat versus 35% fat diets in terms if effect on liver fat, triglycerides adn other metabolic parameters.
    Other Name: Low fat versus extremely low fat Diet
  • Other: Diet
    10 % versus 35 % fat in diet
Active Comparator: Low fat diet is the "drug"
Diet 10% fat versus 35% fat
Interventions:
  • Other: low-fat diet ( Still recruiting )
  • Other: Diet
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
72
December 2016
August 2016   (final data collection date for primary outcome measure)

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

Both
14 Years to 70 Years
No
Contact: Claudia Quittner, RN, BSN, MS 214-648-9296 claudia.quittner@utsouthwestern.edu
Contact: Zahid Ahmad, MD 214-648-2377 zahid.ahmad@utsouthwestern.edu
United States
 
NCT00457938
RO1-074959, DK074959
Yes
Abhimanyu Garg, University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center
  • National Institutes of Health (NIH)
  • Takeda
  • Amylin Pharmaceuticals, LLC.
Principal Investigator: Abhimanyu Garg, MD UT Southwestern Medical Center
University of Texas Southwestern Medical Center
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP