Effect of Increased Free Fatty Acids on Leptin Function

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01520454
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 4
• Duration (Months): 61
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Obese people have elevated levels of the hormone leptin. Despite this, they seem to be resistant to the effects of this hormone, which usually regulates appetite and energy expenditure. This is similar to what happens with insulin levels in the obese. Furthermore, the way lipid ingestion versus lipid infusion may impact novel molecules secreted by tissues commonly affected in insulin resistant states such as liver and muscle have not yet been studied.

The aim of the present study is to investigate the effect of oral vs. different doses of IV lipid administration on molecular parameters related to glucose and energy homeostasis using a randomized, placebo-controlled design.

Additionally, we will examine how increased free fatty acids (FFAs) my impact intracellular leptin signaling such as the STAT3 pathway.

Condition or Disease	Intervention/Treatment	Phase
Obesity; Leptin Resistance	Drug: Saline; Drug: Intralipid; Dietary Supplement: Water; Dietary Supplement: oral fat; Drug: Heparin	N/A

Detailed Description

We propose to test our hypotheses by conducting a non-blinded, interventional study evaluating the effects of acute leptin administration on intracellular leptin signaling pathways after a 6 hour infusion period comparing an oral high fat meal, high fat lipid infusion, low fat lipid infusion, or placebo infusion (saline)iv lipid infusion, placebo (saline) and oral high fat meal. After a screening visit, study participation involves 1 meal pick-up visit, 1 overnight visit, and one 1 follow-up visit. Subjects will be randomized to one of 4 groups: an oral high fat meal, fat emulsion 20% infusion , fat emulsion 10% infusion, and a placebo (saline) infusion infusion and an oral high fat meal.

We plan to screen 100 male and postmenopausal female subjects, with BMI greater than 18 kg/m2, to consent 60 in order to have 32-48 evaluable subjects, 8-12 subjects per group, completing all parts of the study.

The primary study outcome to be evaluated will be the changes in serum concentrations of glucose, hormones influencing metabolism such as insulin, fat-cell-secreted proteins such as leptin, molecules involved in metabolism such as free fatty acids (FFAs), and markers of inflammation such as interleukin (IL)-2 and interferon (IFN)-gamma.

The secondary outcome will be to examine the impacts of increased FFAs on intracellular leptin signaling by phosphorylation of STAT3.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Differential Effects of Oral and Intravenous Lipid Administration on Leptin Signaling
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo IV saline with heparin, oral water	Drug: Saline; IV saline at 0.83 mL/kg/hr for six hours; Dietary Supplement: Water; Water by mouth; Drug: Heparin; Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours; Other Names: anti coated
Experimental: High dose fat solution Intralipid at high dose, with heparin and PO water	Drug: Intralipid; Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours; Other Names: intravenous lipids ; Dietary Supplement: Water; Water by mouth; Drug: Heparin; Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours; Other Names: anti coated
Experimental: Low dose fat solution Low dose IV Intralipid with heparin and PO water	Drug: Intralipid; Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours; Other Names: intravenous lipids ; Dietary Supplement: Water; Water by mouth; Drug: Heparin; Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours; Other Names: anti coated
Experimental: Oral fat Oral fat load with IV saline	Drug: Saline; IV saline at 0.83 mL/kg/hr for six hours; Dietary Supplement: Water; Water by mouth; Dietary Supplement: oral fat; Soybean oil by mouth at 1.25 g/kg x 2 doses; Other Names: soybean oil

Outcome Measures

Primary Outcome Measures

1. Change in Circulating Glucagon-like Peptide-1 (GLP-1) Levels [Baseline to 6 hours]

   The GLP-1 area under the curve (AUC) was calculated from baseline to six hours

2. Change in Circulating Gastric Inhibitory Polypeptide (GIP) Levels [Baseline to 6 hours]

   The GIP AUC fwas calculated from baseline to six hours

3. Change in Circulating Ghrelin Levels [Baseline to 6 hours]

   The Ghrelin AUC was calculated from baseline to six hours

4. Change in Circulating Peptide Tyrosine Tyrosine (PYY) Levels [Baseline to 6 hours]

   The PYY AUC was calculated from baseline to six hours

Secondary Outcome Measures

1. Change in Circulating Glucose Levels [Baseline to 6 hours]

   The Glucose AUC was calculated from baseline to six hours

2. Change in Circulating Insulin Levels [Baseline to 6 hours]

   The Insulin AUC was calculated from baseline to six hours

3. Change in Circulating Leptin Levels [Baseline to 6 hours]

   The Leptin AUC was calculated from baseline to six hours

4. Change in Circulating Adiponectin Levels [Baseline to 6 hours]

   The Adiponectin AUC was calculated from baseline to six hours

5. Phosphorylation of STAT3 Pathways Downstream of Leptin After Lipid Administration [Baseline to 6 hours]

   Intracellular signaling mechanisms downstream of leptin (particularly the STAT3 pathway) in response to lipid administration as represented by phosphorylation (pSTAT3).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age 18-65

Exclusion Criteria:

1. Subjects with a history of any illness, other than obesity, that may affect insulin sensitivity (anemia, infectious diseases, renal or hepatic failure, uncontrolled hypertension, cancer, lymphoma, chronic inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis, states of cortisol or growth hormone excess, alcoholism or drug abuse, and eating disorders).

2. History of diabetes mellitus.

3. Subjects taking any medications that are known to influence glucose metabolism such as glucocorticoids will also be excluded. We will screen for these conditions by means of a detailed history and review of systems and physical examination (see below).

4. Subjects taking any medications known to affect lipids such as statins will also be excluded. We will screen for these similar to above.

5. Cholesterol greater or equal to 250 mg/dL and/or triglyceride levels greater than 500 mg/dL at the time of screening, as determined by laboratory testing.

6. Subjects who have a known history of anaphylaxis or anaphylactoid-like reactions or who have a known hypersensitivity to anesthetic agents such as Lidocaine or Marcaine will be excluded from the study.

7. Hypersensitivity to fat emulsion or any component of the formulation; severe egg or legume (soybean) allergies; pathologic hyperlipidemia, lipoid nephrosis, acute pancreatitis associated with hyperlipemia.

8. Hypersensitivity to heparin or any component of the formulation

9. Severe thrombocytopenia, uncontrolled active bleeding, disseminated intravascular coagulation (DIC); suspected intracranial hemorrhage.

10. Subjects with a history of bleeding dyscrasia, poor wound healing or any medical condition precluding supine position will be excluded from the study.

11. Unable to follow study protocol or any condition that in the opinion of the investigator makes the subject unsuitable for the study.

12. Pregnancy

13. Prior history of gastrectomy, gastric bypass surgery, or other weight loss surgery.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center

Investigators

• Principal Investigator: Christos S Mantzoros, MD, DSc, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mantzoros Lab Home Page

Publications

None provided.

• Responsible Party: Christos Mantzoros, Professor of Medicine, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01520454
• Other Study ID Numbers: 2009P000370
• First Posted: Jan 30, 2012
• Last Update Posted: May 11, 2018
• Last Verified: May 1, 2018

• Keywords provided by Christos Mantzoros, Professor of Medicine, Beth Israel Deaconess Medical Center: Leptin resistance; Free fatty acids; Lipotoxicity
• Additional relevant MeSH terms: Heparin; Soybean oil, phospholipid emulsion

Study Results

Participant Flow

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Period Title: Overall Study
STARTED	9	6	5	6
COMPLETED	9	6	5	6
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat	Total
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses	Total of all reporting groups
Overall Participants	9	6	5	6	26
Age, Customized (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	35.3	29.1	48.6	27.6	35.2
Sex: Female, Male (Count of Participants)
Female	2 22.2%	1 16.7%	1 20%	3 50%	7 26.9%
Male	7 77.8%	5 83.3%	4 80%	3 50%	19 73.1%

Outcome Measures

1. Primary Outcome

Title	Change in Circulating Glucagon-like Peptide-1 (GLP-1) Levels
Description	The GLP-1 area under the curve (AUC) was calculated from baseline to six hours
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

Areas under the curve are presented

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	9	6	5	6
Mean (Standard Deviation) [pM*min]	7147 (3547)	11725 (4799)	11898 (9996)	28060 (8414)

2. Primary Outcome

Title	Change in Circulating Gastric Inhibitory Polypeptide (GIP) Levels
Description	The GIP AUC fwas calculated from baseline to six hours
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

Areas under the curve are presented

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	9	6	5	6
Mean (Standard Deviation) [pM*min/ml]	12894 (8803)	11830 (4516)	19386 (16823)	60559 (36610)

3. Primary Outcome

Title	Change in Circulating Ghrelin Levels
Description	The Ghrelin AUC was calculated from baseline to six hours
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

Areas under the curve are presented

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	9	6	5	6
Mean (Standard Deviation) [pg*min/ml]	172886 (89970)	129451 (46926)	207863 (111684)	166195 (110140)

4. Primary Outcome

Title	Change in Circulating Peptide Tyrosine Tyrosine (PYY) Levels
Description	The PYY AUC was calculated from baseline to six hours
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

Areas under the curve are presented

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	9	6	5	6
Mean (Standard Deviation) [pg*min/ml]	90016 (25755)	65131 (14914)	82474 (21072)	144702 (27466)

5. Secondary Outcome

Title	Change in Circulating Glucose Levels
Description	The Glucose AUC was calculated from baseline to six hours
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

Areas Under the Curve are presented

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	9	6	5	6
Mean (Standard Deviation) [mg*min/dl]	30683 (1249)	28735 (1269)	32566 (1531)	31364 (869)

6. Secondary Outcome

Title	Change in Circulating Insulin Levels
Description	The Insulin AUC was calculated from baseline to six hours
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

Areas Under the Curve are presented

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	9	6	5	6
Mean (Standard Deviation) [mU*min/ml]	1765 (1555)	2072 (970)	2103 (1645)	3021 (1426)

7. Secondary Outcome

Title	Change in Circulating Leptin Levels
Description	The Leptin AUC was calculated from baseline to six hours
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

Areas Under the Curve are presented

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	9	6	5	6
Mean (Standard Deviation) [ng*min/ml]	2050 (2233)	3639 (4470)	5439 (4671)	4973 (5313)

8. Secondary Outcome

Title	Change in Circulating Adiponectin Levels
Description	The Adiponectin AUC was calculated from baseline to six hours
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

Areas Under the Curve are presented

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	9	6	5	6
Mean (Standard Deviation) [ng*min/ml]	1546442 (500930)	2273306 (1068651)	1778846 (857433)	1970601 (961699)

9. Secondary Outcome

Title	Phosphorylation of STAT3 Pathways Downstream of Leptin After Lipid Administration
Description	Intracellular signaling mechanisms downstream of leptin (particularly the STAT3 pathway) in response to lipid administration as represented by phosphorylation (pSTAT3).
Time Frame	Baseline to 6 hours

Outcome Measure Data

Analysis Population Description

The analysis unfortunately can not be performed due to technical reasons as STAT3 was not able to be measured in the samples/not enough volume was left to perform the appropriate tests after trouble-shooting.

Arm/Group Title	Placebo	High Dose Fat Solution	Low Dose Fat Solution	Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours	Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours	Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours	Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
Measure Participants	0	0	0	0

Adverse Events

Time Frame	6 months
Arm/Group Title	Placebo		High Dose Fat Solution		Low Dose Fat Solution		Oral Fat
Arm/Group Description	IV saline with heparin, oral water Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours		Intralipid at high dose, with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours		Low dose IV Intralipid with heparin and PO water Intralipid: Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours Water: Water by mouth Heparin: Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours		Oral fat load with IV saline Saline: IV saline at 0.83 mL/kg/hr for six hours Water: Water by mouth oral fat: Soybean oil by mouth at 1.25 g/kg x 2 doses
All Cause Mortality
	Placebo		High Dose Fat Solution		Low Dose Fat Solution		Oral Fat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		High Dose Fat Solution		Low Dose Fat Solution		Oral Fat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		High Dose Fat Solution		Low Dose Fat Solution		Oral Fat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/5 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.