Evaluation of 3-V Bioscience-2640 to Reduce de Novo Lipogenesis in Subjects With Characteristics of Metabolic Syndrome
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Metabolic syndrome increases the risk for development of heart disease. Another condition
      associated with metabolic syndrome is fatty liver disease which is also referred to as
      nonalcoholic fatty liver disease (NAFLD). Recently, drugs that block fatty acid synthesis
      have been developed to treat cancer. These drugs are now being considered for the treatment
      of NAFLD. A research test designed to measure liver fatty acid synthesis involves consumption
      of a sugary solution and measurement of blood fats over a six-hour period. The present study
      will test the drug 3-V Bioscience-2640 in healthy subjects with characteristics of the
      metabolic syndrome before and after 10 days of treatment to determine if 50 mg/d
      significantly reduces liver fat synthesis and lowers liver fat storage.
    

Detailed description: 
      The drug 3-V Bioscience-2640 has been tested previously in subjects with cancer because the
      lipogenesis pathway is important to the control of some cancer progression. Palmitate
      (C16:0), a saturated, 16-carbon fatty acid is a biomarker of lipogenesis present in blood
      triglyceride (TG), was found to be reduced significantly. A second biomarker of lipogenesis,
      malonyl carnitine, was significantly increased in patients as expected. The present study
      will test a lower dose (50 mg/d) than the maximum dose previously administered. Here, the
      subjects will be men with characteristics of the metabolic syndrome, who are otherwise
      healthy. The focus on subjects with metabolic syndrome is based on the fact that the future
      use of the drug will be in patients with NAFLD who will likely have metabolic syndrome
      characteristics.

      In humans, the primary organ that synthesizes fatty acids is the liver, and this process
      occurs when simple sugars are consumed in the diet. The carbons in the sugars clear to the
      liver and become the molecule acetyl-Coenzyme A, which is the building block of fatty acids.
      The Laboratory of Elizabeth Parks, co-investigator, has developed an oral sugars tolerance
      test (OSTT) to determine the magnitude of liver stimulation of fatty acid synthesis when an
      individual consumes an oral bolus of sugars. This test involves the subject undergoing IV
      infusion with the stable (non-radioactive) isotope (13C1-acetate). The isotope gets
      incorporated into fatty acids that are being synthesized during the course of the infusion
      and when sugars stimulate lipogenesis, the label is more abundance. Those labeled fatty acids
      are detected as present in the blood very low-density lipoprotein (VLDL) component.

      In the present study, the investigators will use this protocol to determine whether 10 days
      of drug treatment (one dose per day) will significantly reduce fasting and
      fructose-stimulated lipogenesis. The study is divided into 3 parts which will support the
      plan for minor adjustments in the dose of drug after the results from the first two research
      subjects are available in order to optimize the suppression of lipogenesis, while also
      minimizing any side effects the drug might have. The study is a repeated-measures design,
      with each subject serving as his own control. The study will be unblinded with respect to the
      research staff working directly with the subjects. However, laboratory personnel who will be
      running the biochemical analyses will be blinded as to whether they are analyzing baseline or
      post-treatment samples.
    

Intervention name(s): 3-V Bioscience-2640
Intervention type(s): Drug
Intervention description(s): Subjects will take a singly daily dose of 3-V Bioscience-26400 before bedtime or 22:30, whichever comes first, for 10 days.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Obesity; Hyperlipidemia; Impaired fasting glucose; Insulin resistance; Hypertension