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

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ClinicalTrials.gov Identifier: NCT02948569
Recruitment Status : Completed
First Posted : October 28, 2016
Last Update Posted : January 4, 2018
Sponsor:
Collaborator:
3V Biosciences, Inc.
Information provided by (Responsible Party):
Elizabeth Parks, University of Missouri-Columbia

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.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Drug: 3-V Bioscience-2640 Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
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
Official Title: Evaluation of 3-V Bioscience-2640, a FASN Inhibitor, to Reduce de Novo Lipogenesis in Subjects With Characteristics of the Metabolic Syndrome
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : December 18, 2017
Actual Study Completion Date : December 18, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Change in liver fat measured by MRI [ Time Frame: After 10 days of treatment ]
    Subject undergoes MRI of abdomen to quantify liver fat.

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02948569


Locations
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United States, Missouri
University of Missouri
Columbia, Missouri, United States, 65201
Sponsors and Collaborators
University of Missouri-Columbia
3V Biosciences, Inc.
Investigators
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Principal Investigator: Elizabeth J Parks, PhD University of Missouri-Columbia

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Responsible Party: Elizabeth Parks, Professor, Nutrition & Exercise Physiology-MED, University of Missouri-Columbia
ClinicalTrials.gov Identifier: NCT02948569     History of Changes
Other Study ID Numbers: 2006432
First Posted: October 28, 2016    Key Record Dates
Last Update Posted: January 4, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Elizabeth Parks, University of Missouri-Columbia:
Obesity
Hyperlipidemia
Impaired fasting glucose
Insulin resistance
Hypertension

Additional relevant MeSH terms:
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Metabolic Syndrome
Syndrome
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases