Clinical trial NCT02948569
Conditions: Metabolic Syndrome
Keywords: Obesity Hyperlipidemia Impaired fasting glucose Insulin resistance Hypertension
Sponsor: University of Missouri-Columbia
Start date: 2017-02-01; Completion date: 2019-01-30
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: Subjects will take a singly daily dose of 3-V Bioscience-2640 before bedtime or 22:30, whichever comes first, for 10 days.
Interventions: intervention 1: 3-V Bioscience-2640
Intervention descriptions: intervention 1: Subjects will take a singly daily dose of 3-V Bioscience-26400 before bedtime or 22:30, whichever comes first, for 10 days.

Protocol documents:
Prot_SAP_ICF_002.pdf: 
 
 
 
 
 
 
 
 
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
 
PROJECT TITLE: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with 
characteristics of the metabolic syndrome" 
 
NCT 02948569 
 
DATE UPLOADED:  March 8, 2017 
 
 


2 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
Primary Investigator  
 
 
 
Co-Investigator__________________ 
Camila Manrique, M.D., Assistant Professor 
 
Elizabeth J. Parks, Ph.D., Professor 
Department of Internal Medicine 
 
 
Department of Nutrition and Exercise Physiology 
Div. of Endocrinology, Diabetes and Metabolism 
Associate Director, Clinical Research Center 
One Hospital Drive, D110 Diabetes Center 
 
School of Medicine, One Hospital Drive, Rm NW406 
University of Missouri   
 
 
 
University of Missouri   
Columbia, Missouri  65212  
 
 
 
Columbia, MO  65212 
Email:  manriquec@health.missouri.edu  
 
parksej@missouri.edu 
Office phone: (573) 882-3818   
 
 
(573) 882-5864 
 
 
 
 
 
 
 
Laboratory NW407, Phone: (573) 884-1708 
 
Sponsor:  3V Biosciences, 1050 Hamilton Court, Menlo Park, CA 94025 
ClinicalTrials.gov number:  NCT02948569 
IND number:  132646 
 
Participating staff: 
Ghassan Hammoud, MD, Data Safety Officer 
Majid Syed-Abdul, MS, Graduate Student 
Nhan Le, BS, Research Specialist II 
Kimberlee Bingham, BS, Research Technician 
Ayman Gaballah, MD, Radiologist 
Ryan Heath, MD, Fellow, Gastroenterology 
Whitney Reist RD, LD, Research Dietitian  
 
Purpose 
The present study is designed to determine whether the drug, TVB-2640 will significantly reduce liver fat synthesis in 
male subjects with characteristics of the metabolic syndrome. 
 
Background 
The continuum of metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) and the more advanced disease of non-
alcoholic steatohepatitis (NASH) can progress to significant liver diseases including cirrhosis and hepatocellular 
carcinoma.  Over the next 5 years, NASH will overtake hepatitis C as the most prevalent liver disease in the U.S.  In 
addition, NAFLD is associated with increased comorbidities including cardiovascular diseases and diabetes.  Obesity and 
the metabolic syndrome [4] are two key risk factors for NAFLD which are characterized as an imbalance in energy 
utilization and storage.  This imbalance leads to dysregulated metabolic pathways and inflammatory responses that drive 
further changes leading to liver damage and comorbid conditions.  There are currently no approved drugs to treat 
metabolic syndrome or NAFLD.  The synthesis of fatty acids in the liver, a pathway termed hepatic de novo lipogenesis 
(DNL), is increased in subjects with metabolic syndrome and NAFLD.  The DNL pathway not only produces fatty acids 
that contribute to elevated liver stores of triglycerides, but the fatty acids that are produced are saturated fatty acid species, 
primarily palmitate (C16:0), which contribute to signaling events that increase liver inflammation.  Therefore DNL is an 
important pathway for therapeutic intervention to reduce the consequences associated with metabolic syndrome and 
NAFLD.  One of the key enzymes in DNL is fatty acid synthase (FASN); this enzyme is solely responsible for 
synthesizing palmitate.  Normal responses to feeding carbohydrate in meals include a transient increase in DNL which is 
dependent on the enzyme FASN.  Using isotopic tracers, it is clear that subjects with NAFLD have higher rates of hepatic 
DNL compared to subjects without fatty liver.  Additionally, NAFLD subjects do not suppress DNL upon fasting unlike 
the subjects without fatty liver.  This observation forms the basis for evaluating the inhibition of FASN, thereby reducing 
DNL, as a potential therapeutic target to reduce fatty liver disease. 
 


3 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
The drug, TVB-2640 has been tested in previous subjects with cancer because the lipogenesis pathway is important to the 
control of some cancer progression.  The drug was shown to have a low side effect profile and the side effects that did 
occur (xeroderma, some hair loss, dry eyes), appeared after 14 days of treatment at doses ranging from 150-450 mg per 
day.  Therefore, the present study will use a shorter duration of treatment (10 days), and choose a starting dose at the 
lower end of this treatment range (50 mg/d). 
 
Specifically, as described in the attached IND application, in 127 cancer patients, at doses of 200 mg, side effects included 
dry eyes, dyspepsia, hair thinning, dry skin, particularly on the hands and feet.  By contrast, at doses of 400-600 mg/d, for 
durations longer than 10 days, corneal edema (n=3) and palmar-plantar erythrodysesthesia (PPE, n=3) were also 
observed.  The corneal edema and PPE were thought to be related to the action of the drug and extended dry eye.  All the 
side effects described above resolved after discontinuation of drug. 
It should be noted that, because previous use of this drug occurred in cancer patients on concurrent treatment with 
paclitaxel, side effects common to paclitaxel were also observed during co-treatment.  These effects, including uveitis, 
fatigue, decreased appetite, and peripheral neuropathy, were not unexpected. 
 
During these studies, a fatty acid biomarker of lipogenesis, found in blood triglyceride (TG) was found to be reduced 
significantly.  The present study will test a lower dose (50 mg/d) in men (no women) 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 non-alcoholic fatty liver disease who will likely have metabolic syndrome 
characteristics. 
 
The Parks lab has developed an oral sugars tolerance test (OSTT) to determine the magnitude of liver stimulation of 
lipogenesis when an individual consumes an oral bolus of sugars [1].  In the present study, we will use this protocol to 
determine whether 10 days of drug treatment will significantly reduce fasting and sugar-stimulated lipogenesis.  The study 
is divided into 3 parts (described below) which will allow us to make minor adjustments in the dose of drug after the first 
six subjects' results are available to optimize the suppression of lipogenesis, while also minimizing any side effects the 
drug might have. 
 
The overall study design is shown in Figure 1 and the timing of the procedures is identical for all three parts of the study.  
The study design is a repeated-measures, 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 personal who will be running the 
biochemical analyses will be blinded to whether they are analyzing baseline or post-treatment samples. 
 
Summary of study objectives 
This study's goal is to identify a drug dose that will effectively lower lipogenesis, while minimizing any side effects.  We 
will start studying two subjects at a dose of 50 mg/day, and  continue at 50 mg/day for the following 4 subjects, closely 
monitoring side effects and drug activity..  Depending on the degree of side effects, effectiveness of the dose in reducing 
lipogenesis, and PK activity for the initial 6 subjects, the dose for the last 6 subjects may be adjusted to a targeted dose 
that will provide the most significant reduction in lipogenesis with the least amount of side effects, if any.  A decision tree 
to serve as the basis for these decisions is presented as Supplementary Figure 1 in the Appendix 
 
We will accomplish the following specific aims: 
Aim 1 (Part 1, subjects 1 and 2).  First, treat two subjects with 50 mg/d of drug for 10 days to preliminarily determine 
the effects of the drug to lower lipogenesis.  Measure fasting and sugar-stimulated lipogenesis before and after treatment, 
while monitoring for side effects.   Hypothesis 1:  A 10d duration of 50 mg/d treatment will lower acute lipogenesis 
stimulated by a bolus of sugars by at least 2% and result in no, or minimal side effects. 
 


4 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
Aim 2 (Part 2, subjects 3-6):  Test an additional 4 subjects according to the results of Part 1.  Hypothesis 2:  Additional 
subjects treated at the same dose will refine the statistical confidence in the observations of Objective 1. 
 
Aim 3 (Part 3, subjects 7-12):  Using the final targeted dose of drug, study 6 subjects using the same in-patient protocol 
as in the other aims.  Hypothesis 3:  Using the final dosing scheme, the last six subjects will demonstrate a significant 
reduction in fasting and stimulated lipogenesis, with the lowest side effects, if any. 
 
 
Study Details 
The sources of research materials will include following items. 
Screening:  Research subject and family medical history, demographic data, vitals, height, weight, BMI calculated, and 
screening laboratory tests including a CMP, hepatitis panel, CBC with differential, concentration of insulin, a lipid panel, 
apolipoproteins B and A1, ECG, and HbA1c.  Demographic data (plus other related data, e.g., emergency contact person), 
smoking history are collected, along with lifestyle information including food/beverage/alcohol intake and physical 
activity will be obtained via questionnaire and a urine sample is used for a general drug screen. 
 
Inpatient CRC studies:  Blood is processed to obtain plasma and the sample used in the isolation and measurement of 
blood metabolites and hormones including glucose, fructose, TG, FFA, ketones, insulin, and for the VLDL-lipoproteins, 
apolipoprotein B100, VLDL-TG concentration, and TG-palmitate lipogenesis.  Once the samples have been processed for 
mass spectrometry and the data acquired, the processed samples will be kept until at least 10 years after publication (the 
stable isotope does not decay and the samples retain their value).  DEXA is used to measure total and regional fat mass 
and fat-free mass, a FibroScan® ultrasound is performed to measure liver elastography (liver stiffness due to fibrosis), and 
MRI is used to assess liver fat.  Indirect calorimetry is performed to measure energy expenditure, and skin oil collected 
(Sebutape®) to measure fatty acid composition.  Table 1 shows how the timeframe over which the 324 ml of blood is 
donated by the subject. 
 
 
 


5 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
Table 1.  Accounting of Blood Usage 
Procedure 
Volume of whole blood (mls) 
Screening blood chemistries 
  40 
V1.  Baseline inpatient study 
100 
V2.  D4 safety blood draw  
  10 
V3.  D6 safety blood draw  
  10 
V4.  D9 safety blood draw  
  14 
V5.  Follow-up inpatient study 
140 
V6.  Follow-up safety blood draw 
  10 
Total for 12 subjects (mls) 
324 
 
Schedule of Events 
Telephone Screening:  The subject will respond to the recruiting flyer or advertisement and answer the waiver of written 
consent and screening questions.  These questions are for preliminary screening only and are not used as study data since 
the data represent self-report.  The questions include queries about health history/habits, age, gender, height, weight, 
tobacco use, medications/supplements, over-the-counter drugs use, illness, and chronic conditions.  The study design is 
described in general terms to subjects, with mention of three factors most likely to impact subject interest in participating.  
These factors include having an IV line, that there are two overnight stays in a hospital research unit, and that the drugs 
may have side effects.  If the subject is interested in being screened for participation, research staff then makes an 
appointment for the subject to come into the CRC for formal consenting, and screening procedures.  The length between 
the screening visit and beginning study procedures may vary according to subject’s availability but will not be longer than 
4 weeks.  For each of the visits shown in Figure 1, the procedures as are described below. 
 
Screening and Consenting Visit:  The first visit to the CRC will include a written formal consent.  We estimate that we 
will have to screen 100 people to find the 12 subjects to do the study.  After signing the consent form, medical 
information is obtained by the nurse including DOB, gender, ethnic/racial category, height, body weight (history of body 
weight), vitals, and medical history (medications use, smoking history and a fasting blood draw (40 mL) is taken to test 
for biochemistries).  An ECG will be performed and read by Dr. Mary Dohrmann, Cardiology.   
 
As soon as the blood biochemistry results are available, the subject is contacted, provided with a copy of the results, told 
whether he is eligible to continue, and asked if they want to participate further.  Staff also ask the subject to describe, in 
their own words, what the baseline visit will be like.  If they agree to participate, an appointment is made for the subject to 
come to the CRC for their overnight baseline visit.  
 
Three days before visit 1, the subject is provided with food and beverages to meet his total energy needs for weight 
stability.  No alcohol will be consumed during this time.  The meals are made up of commercially available foods and the 
composition is based in foods the subject normally consumes. 
 
Baseline Visit 1:  Before arriving to the CRC, the subject will go to Fairview Digestive Health Clinic for a 15 minute 
FibroScan.  If a FibroScan becomes available to be housed in the hospital, then this trip to Fairview would not be 
necessary and the measurement would be made during the inpatient study.  The CRC will begin at 4:00 PM and take 24 
hours and the subject will undergo several procedures.  The first procedure is MRI to assess liver fat content.  Next, after 
returning to the CRC, an IV line will be placed in one of the arms and an isotope (13C1-acetate, 10g/1200 mL half-normal 
saline) will be infused through that IV.  Afterward, the subject will be fed dinner and then undergo a skin test, where a 
piece of tape will be placed on the forehead for 30 minutes to collect oils produced by the skin.  The subject will sleep 
overnight at the CRC.  At 6:00 AM the next morning, the subject will undergo calorimetry and a second IV line will be 
placed in the other arm.  This IV will be used to draw blood.  Following this, he will be asked to consume a sugary drink 
to begin the oral sugar tolerance test (OSTT).  The calorimetry test will be performed again at 9:30 AM and blood will be 
drawn intermittently until 2:00 PM.  The total amount of blood drawn will be 100 mls.  After the final blood draw, the 
subject will be fed lunch and then body composition will be measured by DEXA.  After this, he can leave the CRC.  If all 


6 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
baseline procedures are successful, the subject will be given 10 days of drug to begin taking the first dose that evening.  
Each day, he will take a single pill with water before 10:30 PM (or at bedtime if before 10:30 PM).  The study physician, 
Camila Manrique, MD, will oversee the prescribed dosage the subject will take.  This dosage will be determined in 
consult with the Safety Officer, Ghassan Hammoud, MD, according to the attached Dosing Decision Tree.   
 
The OSTT is a combination of glucose and fructose consumed in 180 ml of water.  Specifically, over a period of 15 min, 
the subject will ingest a "Kool-Aid like" solution of 0.9g/kg fructose and 0.3g/k glucose in water.  After the baseline test is 
completed, the subject takes home all food/beverages that he will consume until he returns for visit 2. 
 
Safety Blood Draw Visits 2 and 3:  As shown in Figure 1, the subject will return to the CRC for a single blood draw in the 
morning, 2 days following the baseline visit.  The subject is instructed not to exercise on this morning before this blood 
draw.  For 12 hours before these visits, he is asked to not eat or drink anything besides water.  Blood will be taken (10 ml) 
and vitals will be checked.  This visit will take about 30 minutes.  On day 4 following the baseline visit, the subject will 
return for safety blood draw visit 3 and the procedures will be the same as safety blood draw visit 2.  At the end of visit 3, 
the subject takes home food to eat until visit 4. 
 
Safety Blood Draw Visit 4:  The subject will return to the CRC for a third safety blood draw and all procedures done at the 
previous safety blood draws will be repeated, with the addition of the skin test.  A small amount of blood will be drawn 
(14 mls).  The subject is asked to not exercise on this morning before this blood draw.  For 12 hours before he comes to 
the visit, the subject is told to not eat or drink anything besides water.  The subject is told not to apply any lotion or skin 
products to the face on the morning of this visit.  This visit will take about 45 minutes.  At the end of visit 4, the subject 
takes food home to keep him weight stable until Follow-up visit 5. 
 
Follow-Up Visit 5:  On the day of the subject’s last dose of medication, he will return to the CRC for the follow-up visit. 
This visit is exactly the same as the baseline visit, however, blood will also be drawn four times during the night to assess 
drug pharmacokinetics.  The subject will come to the CRC at 4:00 PM and stay for 24 hours.  The total blood draw will be 
140 mls.  Following this visit, the treatment portion of this study is over and the subject will discontinue taking the drug. 
 
Safety Blood Draw Visit 6:  Approximately 5-7 days following visit 5, the subject will come into the CRC for a final 
safety blood draw.  The subject is asked to not exercise on this morning before this blood draw.  For 12 hours before he 
comes to the visit, the subject is told to not eat or drink anything besides water.  A small amount of blood will be taken 
(10 mls).  This visit will take about 30 minutes. 
 
 
Human Subjects Involvement and Characteristics 
Recruitment and informed consent:  The study population includes overweight and obese male subjects, aged 35-60y.  The 
recruitment process will include the typical flyers and notices put in public spaces.  The recruitment material will be 
posted around University of Missouri campus, as well as other public places such as swimming pools, churches, and 
grocery stores.  We also plan to use the service called Studykik (https://studykik.com/).  All advertisements will state the 
purpose of the study, eligibility criteria and will tell subjects to call into our laboratory for more information.  During 
these calls, the study will be described briefly.  A checklist will be phone through to perform initial screening for age, 
gender, health status.  Subjects who are eligible by phone screen will be scheduled for a screening visit. 
 
The consent form states the purpose of the study, risks, inconveniences, discomforts, and other important information 
about the study and has been prepared in lay terms so that it is easy to understand.  During the screening visit the form is 
reviewed comprehensively.  The subject will be instructed to ask questions about any words or information that they do 
not clearly understand and questions will be answered by the PI and her staff.  This will enable us to determine the 
subject’s comprehension of the study.  The consent form will be signed before any study procedures are initiated. 
 
 


7 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
Criteria for inclusion 
1.  Men with characteristics of metabolic syndrome  
   a) 
Waist circumference greater than 40 in (102 cm) 
   b) 
Plasma TG greater than 150 mg/dL 
   c) 
HDL cholesterol less than 40 mg/dL 
   d) 
Blood pressure greater than or equal to 130/85 mmHg 
   e) 
Fasting plasma glucose greater than 100 mg/dL but less than 126 mg/dL 
   f) 
Fasting insulin great than 10 uU/mL 
2.  35-60 years of age 
3.  Overweight/obese subjects with BMI 27.1 - 45.0 kg/m2 
4.  Family history of CVD or diabetes 
5.  Habitual diets containing ≥ 5.0% of energy from added sugars 
6.  Creatinine clearance of ≥80 mL/min 
 
Criteria for exclusion 
1.  Diagnosed CVD (unstable angina, NYHA angina > Grade 2), abnormal thyroid function or liver/kidney disease, renal 
dysfunction (defined by GFR <80 mL/min) 
2.  Signs of ascites and signs of hepatic encephalopathy (a score greater than 7 on the Child-Pugh scale, that would place 
     them in either class B or C) 
3.  Chronic skin disorder or treatment for acne 
4.  History of clinically significant dry eye or eye diseases such as glaucoma 
5.  Diabetes defined as fasting glucose ≥ 125 mg/dL or HbA1c ≥ 6.5% 
6.  Habitual diets with low content of added sugars (<5% of total energy) 
7.  Any tobacco use 
8.  Elevated liver enzymes ≥ 3x normal (regional norms ALT <42 U/L, AST <40 U/L, and 
     GGT 8-61 U/L) and extended prothrombin time (PT >11.5 seconds) 
9.  Contraindications of MRI 
10.  Alcohol intake weekly greater than 56 g/week (4 standard drinks/wk). 
11.  Major surgery or donation of blood of >500 mL within the past 8 wks. 
12.  Patients with uncontrolled hypertension, i.e. ≥160/95 mmHg. 
13.  Patients with known cardiac abnormalities such as:  
 - Congenital long QT syndrome 
 - QTc interval > 480 milliseconds 
 - Any cardiac arrhythmia requiring anti-arrhythmic medication. 
14. Patients who have had a myocardial infarction within 12 months of study entry. 
15.  Patients who have a history of coronary artery disease (CAD) e.g. angina Canadian class II to IV [10].  In any subject 
in whom there is doubt, the subject will be excluded. 
16.  Patients with an ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥2 mm).  If in 
any doubt, the patient should have a stress imaging study and exercise ECG and, if abnormal, angiography to define 
whether or not CAD is present. 
17.  Patients with congestive heart failure that meets New York Heart Association class II to IV definitions and/or ejection 
fraction <40% by multiple gated acquisition (MUGA) scan or <50% by echocardiogram and/or magnetic resonance 
imaging (MRI) 
18.  Patients with a history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or 
cardiac arrest, unless currently addressed with an automatic implantable cardioverter defibrillator (AICD). 


8 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
19.  Patients with hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes (if in 
doubt, see ejection fraction criteria above). 
20.  Patients with a history of pneumonitis. 
21.  Individuals taking drugs that are substrates for CYP3A or CYP2C9 and have a narrow therapeutic index.  Examples 
of these drugs include statins (atorvastatin, simvastatin), diuretics (conivaptan, naloxego, eplerenone, tolvaptan), anti-
hypertensives (nisoldipine, felodipine), anti-inflammatories (celecoxib, ebastine), narcotics and sedatives (alfentanil, 
midazolam, triazolam), antipsychotics (buspirone, lurasidone, quetiapine), other lipid-lowering agents (lomitapide) and 
erectile dysfunction medications (avanafil, vardenafil, sildenafil).  Other drugs that would make potential subjects 
ineligible include HIV anti-retrovirals, immunosuppressants and chemotherapeutic agents. 
22.  Individuals who are taking drugs that are strong inhibitors or reducers of CYP3A.  Examples of these drugs include, 
diuretics (conivaptan), antifungals agents and antibiotics (rifampin, itraconazole, ketoconazole, troleandomycin, 
voriconazole, clarithromycin), antidepressants (nefazodone, St. Johns Wort) and antihypertensives (diltiazem). 
 
 
Subject compensation 
Subjects will be compensated based on the amount of their participation in the study as follows: 
$150.00 for consuming the 3 day pretest diet and for baseline visit 1 
$75.00 for participating in safety blood draw visit 2 
$100.00 for participating in safety blood draw visit 3 
$150.00 for participating in safety blood draw visit 4 
$225.00 for consuming the 10-day diet and for participating in follow up visit 5 
$500.00 for participating in safety blood draw visit 6 
Thus, if subjects complete the study, they will be compensated a total of $1,200.00. 
 
Subjects who live 1-2 hours away from Columbia by car will be reimbursed $25 for the screening visit. 
 
Potential risks 
Physical risks may include: 
1.  Intravenous catheterization:  The tests in the present protocol require one IV line to be in for roughly 24 hrs and 
another to be in for roughly 8 hrs.  The standard rule of thumb for hospital infection control is for an IV line to be 
replaced every 48 hrs.  The duration of the IVs in the present protocol is less than this time.  Placement of IV lines 
may cause bleeding, bruising, infection, clotting, pain at the needle site, and/or fainting.  Extravasation of study 
substances could cause swelling and local irritation at the intravenous site.  A black and blue mark may result from 
placement of and IV.  This can be painful, but it carries no significant risks.  Infections from IVs rarely occur. 
2. Blood drawing:  During the screening and safety blood draw visits, blood will be drawn through a needle.  The risk of 
blood drawing may include temporary discomfort from the needle stick, bruising, and rarely, infection.  
3. The total blood loss for the entire study is 324 ml. 
4. Indirect calorimetry:  The inpatient stays include 2 calorimetry tests, which are painless.  However, persons who are 
uncomfortable in confined spaces may find this test slightly stressful. 
5. Stable isotopes:  The stable isotopes received in the IV contain no radioactivity, and have no recognized harmful 
effects.  These compounds are commonplace variants of naturally-occurring compounds (fatty acids, amino acids, 
etc.).  The isotope solution is made by the Investigational Pharmacy and used within 48 hours. 
6. DEXA:  The radiation during DEXA is equivalent to about 2% of the average radiation dose from all sources (natural 
background radiation, consumer appliances, radon gas, medical tests, etc.) that a person in the United States receives 
each year. 
7. Magnetic resonance imaging:  The risks of undergoing an MRI include some psychological stress from a loud, 
banging noise during the scan.  Subjects may experience nervousness from confinement in a tight space 
(claustrophobia).  Magnetic fields to be used in this study present no known hazards to human subjects whose bodies 
do not contain any para-magnetic metals. 


9 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
8. FibroScan:  This ultrasound measurement of the liver involves a probe being placed on the skin above the liver.  
There is no radioactivity associated with this procedure.  A FibroScan test is painless and lasts 15 min.  The subject 
will need to lie very still. 
9. Intake of TVB-2640:  This is an experiment drug which has been shown to have some side effects.  Of the people who 
have taken the drug for 10 days, some have reported, dry skin and dry eyes, sometimes serious enough to stop their 
participation.  A few subjects have reported hair loss or upset stomach.  These side effects have disappeared after 
subjects have stopped taking the drug.  Our study staff will be in contact with subjects by phone and email while they 
are taking the drug to determine if they have any side effects.  We will see them personally three times while they are 
taking the drug to monitor them carefully.  One test we will administer is a skin test, to check for the ability of their 
skin to produce oil. 
10. Sugar test: During the baseline and follow up visit, subjects will be asked to consume a bolus of sugars.  Risks could 
include upset stomach. 
11. Hospital Stays:  During the visits and study, the subject will be restricted to the CRC.  Although quiet leisure activities 
can be provided, confinement to the CRC may be boring or the subject may feel hungry.  Some may find it hard to be 
confined to a hospital bed for the duration of the test. 
12. Sebutape:  This is a piece of tape that is place on the forehead to collect skin oil.  The procedure is noninvasive but the 
tape tugs slightly on the skin when it is removed. 
13. Psychological stress:  The psychological stress from participation in this study is minimal.  However, some of the 
questions about food intake and physical activity may make the subjects feel uncomfortable.  The indirect calorimetry 
test is painless; however, persons who are uncomfortable in confined spaces may find this test stressful.  
14. Loss of confidentiality:  Any time information is collected, there is a potential risk for loss of confidentiality.  Every 
effort will be made to keep subject’s information confidential; however, this cannot be guaranteed.  The information 
collected includes: age, gender, height, body weight, blood pressure, and blood tests results (e.g. glucose, blood fats), 
hepatitis status, urine drug test results, and hormones (insulin).  Finally, the investigator will report information to 
authorities in order to prevent serious harm to the subjects or to others.  If the Investigators suspect child, elder or 
disabled person abuse, they will report such concerns to proper authorities as required by law. 
15. Risks to sperm:  The effects of the DEXA on the male reproductive system are unknown but could cause harm. 
16. Other risks:  There may possibly be other side effects that are unknown at this time.  The complete history of 
experience with this drug in humans is described in the Investigators Brochure which is part of the attached IND 
application. 
 
Protection against risk 
1. Infections from IVs rarely occur.  However, if any signs of infection appear, the IV will be removed and the area 
treated.  Subjects will be counseled to not donate blood for 8 weeks after the study. 
2. Subjects who have donated blood for any other purpose in a short time will be excluded from participation.  The red 
blood cell count (hematocrit) will be measured during screening to rule out anemia and again before the follow-up visit. 
3. A doctor, nurse, or licensed technician will be the one to perform the blood draws. 
4. The protocols that the CRC nurses will follow to reduce risk of infection include:  cleaning the skin thoroughly before 
inserting the IV, securing the IV with tape, covering the site with the clean gauze, and protecting the site using an elastic 
sleeve.  The site is inspected every time blood is drawn with particular attention to any changes in the surrounding skin 
with respect to edema, color, and temperature.  
5. The foods to be consumed will be made of commercially-available ingredients and pose no foreseeable risk.   
6. Subjects who participated in any other research study or medical procedure involving ionizing radiation exposure 
greater than a chest X-ray in the past 12 months will be excluded. 
7. Subjects will be told that they may refuse to answer any questions, take a break, or stop their participation at any time. 
8. Subjects will be allowed to practice wearing the plastic hood used during the calorimetry test during the screening visit. 
 
Subject safety procedures 
These procedures are divided into two parts:  1) Determination of eligibility and 2) on-study safety monitoring.  After 
screening, subject eligibility will be determined by Drs. Hammoud and Manrique, in consult with Dr. Parks.  Once 
subjects are entered into the study, the clinical trial manager will coordinate the safety visits and send the blood chemistry 


10 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
results by email to Dr. Manrique, who will review them and document her response by email to the coordinator.  If she 
has any question, she may also consult Dr. Hammoud to discuss a result.   
 
Procedures to maintain confidentiality 
The health history form and all subject screening and experimental data and pertinent medical paper records will be 
placed in individual files and coded for de-identification.  This information will only be accessible to the principal 
investigator, co-investigator, or approved research personnel.  All records will be kept in a locked filing cabinet, which 
only the research personnel have access to.  Computerized records of experimental data will be similarly coded and will 
be maintained on a password secure system.  The only confidential information to be disclosed would relate to the 
subject’s medical history.  The purpose of obtaining a careful medical history is to verify that the patient meets the 
inclusion/exclusion criteria.  All medical and biographical information will be held in strict confidentiality and no 
disclosures of personal identity will be made unless specifically requested by the subject.  Copies of signed consent forms, 
as well as the experimental log book, are kept in a locked file cabinet in the laboratory.  Only subject ID numbers are used 
to also insure confidentiality.  Participants will not be individually identified in any publications.  The participants’ right 
to privacy will be protected to the highest extent possible. 
 
Protection of materials, and privacy 
All sample tubes are coded to conceal the subjects' identities and no identifying information is present on the tubes.  They 
are labeled with the subject's three-letter code identifier and the date.  No tools (e.g., cell lines, probes, etc) will be 
generated from any of this material.  The study will be conducted in accordance with Good Clinical Practice and HIPAA 
guidelines.  Only the Investigators and study coordinator will have access to the codes.  Aside from the sample sent to the 
Sponsor (3V Biosciences) the samples will not be shared with other investigators within the University of Missouri or 
outside the University.  No identifying information will be shared or reported in any publication. 
 
Potential benefits to human subjects and others 
The research plan tests whether the drug will lower liver fat in men with risks for future nonalcoholic fatty liver disease.  
Development of such a drug would aid the millions of U.S. citizens who suffer from this condition.  There is no direct 
benefit for the subjects and all study procedures are voluntary.   
 
Reducing risk in participants 
The PI and Drs. Camilla Manrique will monitor all procedures and the study results.  The PI will report adverse events to 
the IRB.  Dr. Ghassan Hammoud is the safety officer.  The special precautions are as follows: 
1. 
The subjects will be closely monitored at the CRC by nurses. 
2. 
Standard aseptic technique, frequent monitoring of vital signs, and visual inspection of the IV line sites will be 
followed during IV line placement and blood sampling. 
3. 
The isotopes used are purchased to be consumed and prepared as sterile for administration via IV.  The isotope 
solution is made by the Investigational Pharmacy and used within 48 hours. 
4. 
The tests in this study have been designed for research, not for medical purposes.  The subjects will be informed in 
the event that the PI or Drs. Camila Manrique or Ghassan Hammoud discovers a possible abnormality; the subject 
will be given a copy of the screening results and advised to consult with their primary care physician to discuss 
further tests and/or follow-up. 
5. 
The procedures to maintain confidentiality have been discussed above in the section “privacy.” 
6. 
The results of any test or procedure done in this study will follow internal laboratory controls. 
7. 
This study does not involve vulnerable populations. 
8. 
To minimize any risks, BLS certified personnel will be present during all experiments.  Venous cannulation will be 
performed under sterile conditions only by research personnel with required training and experience with these 
techniques.  In case of emergency, during study visits and experimental measurements, a physician investigator 
and/or research nurse will be present: the University Hospital has in place a system to allow for a code Blue (i.e., 
cardiac arrest) by dialing 882-7979 in which trained hospital personnel will respond.   
 
 
 


11 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the 
metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
Sample size 
The present project is a pilot study to allow determination of an appropriate dose of drug for a future study.  We will also 
use the variability observed here to calculate a future sample size.  The mass spectrometry lipogenesis measurement 
produces final data that are in units of percentage, reflecting the fraction of palmitate secreted by the liver in TG that are 
derived from sugars.  Our past research has shown that the lipogenesis measure is highly reproducible within a subject 
with a relative 1-2% variance between days.  For example, one subject's fasting lipogenesis was measured on 3 different 
occasions and found to be 7.8%, 9.6%, and 10.1% (mean 9.2%, SD 1.2%).  In the present study, with 12 subjects we 
should be able to detect as little of an absolute treatment difference of 2% between baseline (e.g. 9.2%) and follow-up 
lipogenesis (down to 7.2%), with a SD of that differences as small as 2%, SD 1.4% (=90%) or the same effect of the 
drug of 2%, with a SD of 1.4% with 8 subjects (=80%). 
 
Adverse events and emergencies 
Any serious adverse events will be reported directly to the IRB.  A detailed report of all adverse events will be submitted 
to the IRB and a determination of related or unrelated event will be made.  In case of emergency, the University Hospital 
has in place a system to allow for a code Blue (i.e., cardiac arrest) by dialing 882-7979 in which trained hospital personnel 
will respond.  The CRC Research Nurses are certified in BLS and ACLS.  The nurse in charge of the study will activate 
the Code Response and initiate Basic Life Support until the Code Blue Team arrives. 
 
Statistical analysis and calculations 
StatView®, 5.0.1 software (version 2008) was used when a paired sample t-test was performed.  Regression analysis, one-
factor analysis of variance (ANOVA), two-factor ANOVA, and Holm-Sidak post hoc analyses were performed using the 
statistical package for the social sciences (SPSS®, version 24, 2016).  Pearson correlation analysis was performed using 
SPSS® (version 24, 2016).  HOMA-IR was calculated as [(glucose in mg/dL * insulin in U/mL)/405. 
 
Reference 
1. 
Parks EJ, Skokan LE, Timlin MT, Dingfelder CS:  Dietary sugars stimulate fatty acid synthesis in adults.  
2546703  J Nutr, 138(6):1039-1046, 2008 
 


12 | P a g e  
UNIVERSITY OF MISSOURI IRB PROTOCOL: Project 2006432 
Project Title: "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects with characteristics of the metabolic syndrome" 
Version 6 Date:  March 8, 2017 
 
 
 


 
 
 
 
UMC, HS IRB: CONSENT  
 
 
 
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CONSENT FORM TO PARTICIPATE IN A RESEARCH STUDY 
 
 
INVESTIGATORS' NAMES:  Camila Manrique, MD, Ghassan Hammoud, MD, and  
                                             Elizabeth J Parks, PhD, at the University of Missouri in Columbia, MO 
STUDY STAFF:  Kimberlee Bingham, BS 
Majid Syed-Abdul, MS   
Nathan Le, BS 
MU PROJECT #:  2006432 
 
CLINICALTRIALS.GOV NUMBER:  NCT02948569 
STUDY TITLE:  "Evaluation of TVB-2640, a FASN Inhibitor, to reduce de novo lipogenesis in subjects 
with characteristics of the metabolic syndrome" 
 
 
INTRODUCTION 
This consent may contain words that you do not understand.  Please ask the investigator or the study 
staff to explain any words or information that you do not clearly understand.  This project is a research 
study.  Research studies include only people who choose to participate.  As a study participant 
you have the right to know about the procedures that will be used in this research study so that 
you can make the decision whether or not to participate.  The information presented here is 
simply an effort to make you better informed so that you may give or withhold your consent to 
participate in this research study.  Please take your time to make your decision.  This study is 
being sponsored by the Company, 3V Biosciences, who has developed an investigational drug to 
treat liver disease in overweight people.  This drug is not approved by the FDA at this time.  One 
of the Co-Investigators, Elizabeth Parks, consults for this company and therefore she received 
financial compensation from the company sponsoring this research.  Elizabeth Parks has 
designed the study and a physician, Dr. Manrique will be conducting it. 
 
What is this study about?  People who are overweight can begin to store fat in their liver.  This fat is 
made from dietary sugar and can cause the liver to not work well.  You are being asked to take 
part in this study because your body weight increases the likelihood that your liver will make fat.  
In order to participate in this study, it will be necessary to give your written consent. 
 
The following definitions may help you understand this study: 
• 
“Researchers” means the study doctor and research personnel at the University of Missouri. 
• 
“Stable isotopes” are naturally occurring elements used to help us trace sources of fat in the 
             blood.  Stable isotopes are not radioactive. 
 
WHY IS THIS STUDY BEING DONE AND HOW MANY PEOPLE WILL TAKE PART? 
The company 3V Biosciences has developed an investigational drug called TVB-2640.  This drug is not 
approved by the FDA at this time.  In preliminary studies, this drug has been shown to lower liver fat 
production but the ideal dose for its use has not been decided.  The purpose of this study is to test the 
drug in overweight men, to determine the appropriate dose.  The information from this study will enable 
future studies to test the drug’s effects in patients with liver fat due to disease.  The tests performed are 
not part of your standard medical care.  Up to 100 people will be screened to find the 12 people who will 
take part in this study. 
 


 
 
 
 
UMC, HS IRB: CONSENT  
 
 
 
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WHAT IS INVOLVED IN THE STUDY AND HOW LONG WILL I PARTICIPATE? 
This research is measuring how the drug may improve liver health.  You will be screened to find out if 
you are eligible to participate.  As shown below, over 20-day period this research includes 2 inpatient 
study visits, 4 safety blood draws, and a daily dose of the drug for 10 days. 
 
STUDY TIMELINE 
The following paragraphs describe the schedule for the study screening visit and five study visits. 
 
SCREENING VISIT 
To help decide if you qualify to be in this study, the researchers will ask you questions about your health, 
including medications you take and any surgeries you have had.  This visit is located at the Clinical 
Research Center (CRC).  The CRC is on the 5th floor of the University Hospital and has clinic rooms 
specially designed for research.  You will come to the CRC after fasting overnight for 12 hours (no food 
or drink, except water).  This visit will take 1 hour and you are welcome to bring a family member or close 
friend to this visit. 
 
Research staff will meet with you to review the study procedures, answer questions, sign this consent 
form and review your medical history.  A small amount of blood will be drawn (about 2.5 tablespoons) to 
check your general health which includes a test for hepatitis as well as a measurement of your fasting 
blood sugar to ensure you are not diabetic.  Your urine will be tested for drugs.  Your height, weight, and 
blood pressure will be measured and you will be given a chance to learn about a procedure called 
calorimetry, which we use to measure how many calories your body burns.  If you enter the study, this 
technique will be performed four times.  Within a week after the screening visit, you will receive the 
results of all screening tests and someone on the study team will go over the results with you.  Since this 
is not a treatment study, these lab tests are not being used for standard medical care.  You will be given 
a copy of the results which you can share with your primary physician. 
 
If your screening results qualify you to be in the study, and if you are interested in proceeding with the 
study, you will be scheduled for a second, baseline visit.  Again, you will come to the CRC at the hospital 
and parking will be provided if needed.  For 3 days before this baseline visit, you will be provided a 3-day 
controlled diet which is made fresh and based on foods you normally prefer.  You must consume only 
these meals, all of the food provided, and no other food.  You may not consume alcohol between days -2 
and 13 of the study. 
 
BASELINE VISIT 1:  On the day of your first overnight hospital test, you will come into the CRC at 4:00 PM.  
This visit will take about 24 hours and you will undergo several procedures.  The first procedures include 
assessments of your liver health.  This will include Magnetic Resonance Imaging (MRI) and also, 
potentially, a procedure called the FibroScan.  These, and all the procedures are described in detail 
below.  When you return to the CRC after your scan, an IV line will be placed in a vein in one of your 
arms.  Next, an IV solution is infused.  This solution is called an isotopic tracer and it will continue until 2 
PM the next day.  You will be fed dinner and then undergo a skin test in which a piece of tape will be 
placed on your forehead for 30 minutes to collect a sample of the oils produced by your skin.   
 
You will then sleep overnight in the CRC.  At 6 AM the next morning, you will arise and wash up.  Then, a 
second IV line is placed in your other arm and this one will be used to draw blood.  You will undergo a 
procedure called calorimetry, which measures the amount of calories you burn.  You will then consume a 


 
 
 
 
UMC, HS IRB: CONSENT  
 
 
 
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sugary drink and blood will be drawn off and on until 2 PM.  You will undergo calorimetry a second time.  
After the final blood draw, you will be fed lunch and undergo a procedure called a DEXA scan.  The 
DEXA scan measures your body composition.  After this you will be discharged and can go home. 
 
If all baseline procedures are successful, you will begin the drug treatment regimen for the next 10 days.  
You will take a single daily dose of the drug orally before bedtime or 10:30 PM, whichever comes first.  
The physician assigned to this study will oversee the prescribed dosage you are instructed to take. 
 
SAFETY BLOOD DRAW VISIT 2:  The morning of this visit, please do not exercise, and for 12 hours before 
the visit, do not use caffeine and vitamin supplements.  You will come into the CRC after fasting 
overnight for 12 hours - no food or drink, except water after 7 PM.  A small amount of blood will be taken 
(about 1 tablespoon) and we will check your weight, blood pressure, heart rate, and temperature. This 
visit will take about 30 minutes. 
 
SAFETY BLOOD DRAW VISITS 3:  This visit is the same as visit #2 above.  A small amount of blood will be 
taken (about 1 tablespoon). 
 
SAFETY BLOOD DRAW VISITS 4:  This visit is the same as visit #2 above with the addition of a collection of 
skin oils. A piece of tape will be placed on your head for 30 minutes to collect the oils produced by your 
skin.  The morning of this visit, do not apply any lotion or skin products on your face.  A small amount of 
blood will be taken (about 1 tablespoon).  This visit will take about 1 hour. 
 
FOLLOW-UP VISIT 5:  Just as you did for the baseline visit, you will come in to the CRC at 4 PM and the 
procedures will be the same.  However, in this visit, blood will also be drawn 4 times during the night.  
This visit will take 24 hours and the total blood draw will be about 2 oz or about 2 tablespoons.  Following 
this visit, the treatment portion of this study is over and you will discontinue taking the drug. 
 
SAFETY BLOOD DRAW VISIT 6:  Approximately 5-7 days following visit 5, you will come into the CRC for 
final safety blood draw (1 tablespoon).  The same procedures will be done at this visit as with safety 
visits 2 and 3.  This visit will take about 45 minutes. 
 
WHAT ARE THE PROCEDURES AND RISKS OF BEING IN THIS STUDY? 
STUDY DRUG 
The study drug, TVB-2640, has been given in preliminary studies for 3 weeks to 2 months in duration.  Side 
effects were seen in some subjects after 21 days on the drug and included dry and sore eyes, some hair loss, 
and upset stomach.  Also, dry skin on the hands and feet which can also feel sore.  All side effects went away  
after the subjects stopped taking the drug.  These side effects were seen at higher doses than will be used 
here, and when the drug was given for longer durations.  In the present study, you will take the drug for 10 
days.  Even so, you will be monitored closely and blood samples will be taken every couple of days to 
document the drug’s effects.  If you notice any side effects such as dry skin, nausea, or eye problems, please 
notify the study staff immediately.  If your skin gets dry you will be provided with lotion to reduce this side 
effect.  Additionally, it is unknown whether this drug has any effects on a man’s ability to reproduce.  We 
advise all subjects to use contraception (condoms) during the duration of this study. 
 
STUDY DIET:  FOOD AND BEVERAGES 


 
 
 
 
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If you participate in the study you will be provided all your food during the 10 days you are taking the 
drug.  This food is commercially available (bought from HyVee) and the meals are made both fresh and 
also made up of some frozen meals.  When you come in for the safety blood draws, you will be given the 
food in a cooler to take home.  If you prefer, you may be provided a couple of cans of soda to drink 
during this time (no other soda than these can be consumed).  Otherwise, only water, tea, and coffee are 
allowed (cream and any kind of sweetener is allowed).  No additional milk shakes, protein shakes, or 
energy drinks should be consumed during this study. 
 
It is advised that if you have a special event coming up in the next month (wedding, vacation travel, etc.) 
that you not participate in the study at this time.  You should not consciously change your physical 
activity while you are in the study.  In other words, if you would like to join a gym or begin exercising 
more, we ask that you wait until the study is over before you do this. 
 
CALORIMETRY 
This test measures how many calories your body uses.  This procedure will be performed at visit 1 and 
visit 5.  Calorimetry requires resting quietly on your back for 20-30 minutes under a large, clear, plastic 
hood.  You will breathe room air normally and your breath goes into an analyzer to measure what you 
breathe out.  The test is painless; however, persons who are uncomfortable in confined spaces may find 
this slightly stressful.  You will get a chance to familiarize yourself with this procedure during screening. 
 
MEASUREMENT OF BODY FAT AND MUSCLE BY DEXA SCAN   
This test will be performed at visit 1 and 5.  A DEXA (dual energy x-ray absorptiometry) scan is a 
procedure to measure your body composition - how much fat and muscle your body has.  It is a type of x-
ray machine with a moving arm.  This procedure involves lying on a table for 20-30 minutes while the 
DEXA machine passes over your body.  Although you will need to remain very still and quiet, you will feel 
nothing and should have no discomfort.  If you have participated in any other research study involving 
ionizing radiation exposure (x-rays) in the past 12 months, discuss this with the Investigator to determine 
if you are eligible to participate in this study.  You will be exposed to a small radiation dose which is 
about 2% of the average radiation dose from all sources (natural background radiation, consumer 
appliances, radon gas, medical tests, etc.) that a person receives in the United States receives each 
year.  However, radiation effects add up.  If you need an x-ray in the next year, you should inform your 
doctor of your participation in this study. 
 
MEASUREMENT OF LIVER FAT BY MRI  
This test will be performed at visit 1 and 5 at either the department of Radiology at University Hospital or 
at the Missouri Imaging Center at South Providence Medical Park.  Transportation will be provided.  MRI 
(magnetic resonance imaging) is a technique used to measure the amount of fat present in your liver.  
The risks of undergoing an MRI could include some psychological stress from a banging noise during the 
scan.  Subjects may experience nervousness from confinement in a tight space (claustrophobia).  
Magnetic fields to be used in this study have no known hazards to human subjects whose bodies do not 
contain any magnetic metals (see below for protection from risks).  If you feel anxious, you can stop the 
procedure at any time.  You may experience some discomfort and fatigue from lying still during scanning.  
You will be questioned using a standardized interview about whether you have a heart pacemaker, 
metallic objects, vascular clips, electrodes, cochlear implants, neurostimulators, shunts, heart valve 
implants, penile implants, vascular filters, rods & screws, post CABG pacer wires, colored contact lens, 
dental prostheses, limb prostheses, eye prostheses, shrapnel, metal in head, eye, or skin, and 


 
 
 
 
UMC, HS IRB: CONSENT  
 
 
 
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embolization coils.  If such devices cannot be removed safely, you will be excluded from the study.  We 
have a mock scanner to allow you to practice the procedure.  When the scan is occurring, the radiology 
technician is in constant contact with you through head phones. 
 
FIBROSCAN 
This procedure is designed to measure the stiffness of your liver.  It requires that you lie still on your back 
while a technician places a wand on your skin over your ribs.  The test is painless and takes 15 to 30 
minutes.   
 
SKIN OIL COLLECTION 
One of the side effects of the drug can be dry skin.  To monitor this side effect, a small sample of skin 
oils will be collected from your forehead using a piece of tape that is placed on the skin for 30 minutes.  
There are no risks associated with this procedure. 
 
RISKS OF BLOOD DRAWING  
During screening and at visits 1-5, you will have blood drawn through a needle.  Risks associated with 
drawing blood from your arm include minimal discomfort and/or bruising.  Infection, excess bleeding, 
clotting, and/or fainting also are possible, although unlikely.  As a result of your participation in this study 
you will have donated blood.  If you wish to participate in other research after you finish this project, you 
should let the investigator know that you have given about 6 oz (or about 3/4 cup).  Your blood volume 
will be checked during screening to make sure that it is in safe limits. 
 
INTRAVENOUS CATHETERIZATION 
During baseline visit 1 and follow up visit 5, you will have an IV line placed that is identical to the IV that a 
person receives when admitted to the hospital.  While IVs are normally safe and painless, there is always 
a very small risk of infection, bleeding, or bruising associated with the catheter.  Should the IV fall out of 
the vein, it is possible that some of the liquid will go into the skin rather than the vein.  This may result in 
swelling and pain around the area of the IV, and the IV would have to be placed in a different location on 
the arm or hand.  The IV lines will be in for about 20 hours.  The protocols that the CRC nurses follow to 
reduce risk of infection include:  cleaning the skin thoroughly before IV placement, securing the IV with 
tape, covering the site with clean gauze, and protecting the site using an elastic sleeve.  The site is 
inspected at each blood draw – with particular attention paid to any changes in the surrounding skin. 
 
HOSPITAL STAYS  
During your visit you will be restricted to the CRC.  Although quiet leisure activities can be provided, 
confinement to the CRC may be boring or you may feel hungry.  You may move about your assigned 
hospital room and use the facilities as needed, unless the test being performed requires bed-rest.  Some 
people may find it hard to be confined to a hospital bed for the duration of the test.  For the reasons 
stated above the investigator will observe you closely while giving the treatment described and, if you 
have any worrisome symptoms or symptoms that the investigator or her associates have described to 
you, notify the investigator immediately.  Investigator’s telephone number is (573) 529-1141.  For more 
information about risks and side effects, ask the investigator or contact study coordinator, Kimberlee 
Bingham at 573-884-1708. 
 
WHAT WILL BE MY RESPONSIBILITIES DURING THE STUDY AND ARE THERE BENEFITS? 


 
 
 
 
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While you are part of this study, the researchers will follow you closely to determine whether there are 
problems.  It is your responsibility to do the following: 
• 
Ask questions about anything you do not understand. 
• 
Keep your appointments. 
• 
Follow the researchers’ instructions, particularly in consuming the medication. 
• 
Let the researchers know if your telephone number or address changes. 
• 
Tell the researchers before you take any new medication, even if it is prescribed by another 
doctor for a different medical problem, or purchased over the counter. 
• 
Report to the researchers any injuries or illnesses while you are on the study, even if you do not 
think they are related. 
 
If you agree to take part in this study, there will be no direct medical benefit to you.  You may expect to 
benefit from taking part in this research to the extent that you are contributing to medical knowledge.  
You will receive the results of all of your tests.  We hope the information learned will benefit others in the 
future. 
 
WHAT ARE THE COSTS? 
You will not be charged for any procedures that are part of this research study.  Parking will be provided 
but there is no compensation for travel to our facilities or for childcare during this study. 
 
WILL I BE PAID FOR PARTICIPATING IN THE STUDY? 
You will be compensated a total of $1,200 for completing this study as follows:  $150 will be given for 
baseline visit 1; $75 will be given for safety visit 2, $100 for safety visit 3 and $150 for visit 4, $225 for 
consuming the 14-day diet and completing follow-up visit 5, and $500 for the final safety blood draw. 
 
WHAT OTHER OPTIONS ARE THERE? 
You do not have to participate in this study. 
 
WHAT ABOUT CONFIDENTIALITY? 
Information produced by this study will be stored in the investigator’s file and identified by a code number 
only.  The code key connecting your name to specific information about you will be kept in a separate, 
secure location.  Information contained in your records may not be given to anyone unaffiliated with the 
study in a form that could identify you without your written consent, except as required by law.   
 
It is possible that your medical and/or research record, including identifying information, may be 
inspected and/or copied by the study sponsor (and/or its agent), the Food and Drug Administration 
(FDA), federal or state government agencies, MU Health Sciences IRB, or hospital accrediting agencies, 
in the course of carrying out their duties.  If your record is inspected or copied by the study sponsor 
(and/or its agents), or by any of these agencies, the University of Missouri will use reasonable efforts to 
protect your privacy and the confidentiality of your medical information.  The results of this study may be 
published in a medical journal or used for teaching purposes.  However, your name or other identifying 
information will not be used in any publication or teaching materials without your specific permission. 
 
WHAT IF I AM INJURED? 
In the event the research results in injury, the Sponsor agrees that it, and not Institution, will be 
responsible for the costs of diagnosis, care and treatment of any undesirable side effects, adverse 
reactions, illness or injury.  The study staff will coordinate your care, should you need it.  In the event you 


 
 
 
 
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have suffered injury as the result of participation in this research program, you are to contact the Risk 
Management Officer, telephone number (573) 882-1181, at the Health Sciences Center, who can review the 
matter and provide further information.   
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
Participation in this study is voluntary.  You do not have to participate in this study.  Your present 
or future care will not be affected should you choose not to participate.  If you decide to participate, you 
can change your mind and drop out of the study at any time without affecting your present or future care 
at the University of Missouri.  Leaving the study will not result in any penalty or loss of benefits to which 
you are entitled.  In addition, the investigator of this study may decide to end your participation in this 
study at any time after she has explained the reasons for doing so and has helped arrange for your 
continued care by your own doctor, if needed.  You will be informed of any significant new findings 
discovered during the course of this study that might influence your health, welfare, or willingness to 
continue participation in this study. 
 
The Data Safety Monitor for this study is Dr. Ghassan Hammoud, a liver expert.  He will be reviewing the 
blood draw values throughout the time you are participating to monitor your safety.  Our study staff will 
tell you about the new information from this or other studies that may affect your health, welfare, or 
willingness to continue participation in this study.  A description of this clinical trial is available on 
www.ClinicalTrials.gov, as required by U.S. law.  This Web site will not include information that can 
identify you.  At most, the Web site will include a summary of the results.  You can search this Web site 
at any time. 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
If you have any questions regarding your rights as a participant in this research and/or concerns about 
the study, or if you feel under any pressure to enroll or to continue to participate in this study, you may 
contact the University of Missouri Institutional Review Board (which is a group of people who review the 
research studies to protect participants’ rights) at (573) 882-3181.  You may also contact the Research 
Participant Advocate (RPA) at (573) 884-1925 or (888) 280-5002 (toll-free).  If you prefer email, you can 
reach the Advocate at somrpa@missouri.edu.   
 
You may ask more questions about the study at any time.  For questions about the study or a research-
related side effects or injury, contact Dr. Camila Manrique at (573) 882-2273.  A copy of this consent 
form will be given to you to keep. 
 
SIGNATURES 
I confirm that the purpose of the research, the study procedures, the possible risks and discomforts as 
well as potential benefits that I may experience have been explained to me.  Alternatives to my 
participation in the study also have been discussed.  I have read this consent form and my questions 
have been answered. 
 
My signature below indicates my willingness to participate in this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject name (print)    
 
          Subject signature 
 
Date 
 
 
Time 
 


 
 
 
 
UMC, HS IRB: CONSENT  
 
 
 
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Staff obtaining consent (print)                      Staff signature  
 
Date 
 
 
Time