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Evaluation of 3-V Bioscience-2640 to Reduce de Novo Lipogenesis in Subjects With Characteristics of Metabolic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02948569
Recruitment Status : Completed
First Posted : October 28, 2016
Last Update Posted : January 4, 2018
Sponsor:
Collaborator:
Sagimet Biosciences Inc.
Information provided by (Responsible Party):
Elizabeth Parks, University of Missouri-Columbia

Tracking Information
First Submitted Date  ICMJE October 18, 2016
First Posted Date  ICMJE October 28, 2016
Last Update Posted Date January 4, 2018
Actual Study Start Date  ICMJE February 1, 2017
Actual Primary Completion Date December 18, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2016)
Change in hepatic lipogenesis [ Time Frame: After 10 days of treatment ]
Subject undergoes a stable isotope infusion followed by blood draws. Plasma lipid samples are measured by gas chromatography/mass spectrophotometry.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2016)
  • Change in liver fat measured by MRI [ Time Frame: After 10 days of treatment ]
    Subject undergoes MRI of abdomen to quantify liver fat.
  • Change in skin sebum production [ Time Frame: After 10 days of treatment ]
    Subjects will undergo a skin test in which 4 pieces of clear Sebutape will be placed on the forehead for 30 minutes. The tape is then removed with a sample of sebum (skin oils). The tape is shipped to a lab for processing where lipid content will be analyzed.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of 3-V Bioscience-2640 to Reduce de Novo Lipogenesis in Subjects With Characteristics of Metabolic Syndrome
Official Title  ICMJE Evaluation of 3-V Bioscience-2640, a FASN Inhibitor, to Reduce de Novo Lipogenesis in Subjects With Characteristics of the Metabolic Syndrome
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
There is only one treatment arm in this study and the subjects are all aware that they are on active treatment. The outcomes assessor will be masked as to which data are from the baseline visit and which are from the follow-up visit. In other words, data will be analyzed in the lab in a blinded fashion as to whether the samples are from before or after treatment.
Primary Purpose: Treatment
Condition  ICMJE Metabolic Syndrome
Intervention  ICMJE Drug: 3-V Bioscience-2640
Subjects will take a singly daily dose of 3-V Bioscience-26400 before bedtime or 22:30, whichever comes first, for 10 days.
Study Arms  ICMJE Experimental: 3-V Bioscience-2640
Subjects will take a singly daily dose of 3-V Bioscience-2640 before bedtime or 22:30, whichever comes first, for 10 days.
Intervention: Drug: 3-V Bioscience-2640
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 2, 2018)
13
Original Estimated Enrollment  ICMJE
 (submitted: October 27, 2016)
12
Actual Study Completion Date  ICMJE December 18, 2017
Actual Primary Completion Date December 18, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Men with characteristics of metabolic syndrome

    1. Waist circumference greater than 40 in (102 cm)
    2. Plasma TG greater than 150 mg/dL
    3. HDL cholesterol less than 40 mg/dL
    4. Blood pressure greater than or equal to 130/85 mmHg
    5. Fasting plasma glucose greater than 100 mg/dL but less than 126 mg/dL
    6. Fasting insulin great than 10 microunits/mL
  2. 35-60 years of age
  3. Overweight/obese subjects with BMI 27.1 - 35.0 kg/m2
  4. Family history of cardiovascular disease or diabetes
  5. Habitual diets containing ≥ 5.0% of energy from added sugars
  6. Creatinine clearance of ≥80 mL/min

Exclusion Criteria:

  1. Diagnosed cardiovascular disease (unstable angina, New York Heart Association angina > Grade 2), abnormal thyroid function or liver/kidney disease, renal dysfunction (defined by a glomerular filtration rate <80 mL/min)
  2. Chronic skin disorder or treatment for acne
  3. History of clinically significant dry eye or eye diseases such as glaucoma
  4. Diabetes defined as fasting glucose ≥ 125 mg/dL or HbA1c ≥ 6.5%
  5. Habitual diets with low content of added sugars (<5% of total energy)
  6. Any tobacco use
  7. Elevated liver enzymes ≥ 3x normal (regional norms Alanine transaminase <42 U/L, aspartate aminotransferase <40 U/L, and gamma-glutamyl transferase 8-61 U/L)
  8. Contraindications of MRI
  9. Alcohol intake weekly greater than 56 g/week (4 standard drinks/wk).
  10. Major surgery or donation of blood of >500 mL within the past 8 wks.
  11. Patients with uncontrolled hypertension, i.e. ≥160/95 mmHg.
  12. Patients with known cardiac abnormalities.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 35 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02948569
Other Study ID Numbers  ICMJE 2006432
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Elizabeth Parks, University of Missouri-Columbia
Study Sponsor  ICMJE University of Missouri-Columbia
Collaborators  ICMJE Sagimet Biosciences Inc.
Investigators  ICMJE
Principal Investigator: Elizabeth J Parks, PhD University of Missouri-Columbia
PRS Account University of Missouri-Columbia
Verification Date January 2018

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