An interventional study of Saline and Intralipid in Obesity and Leptin Resistance, sponsored by Beth Israel Deaconess Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-05-11.
Sponsored by Beth Israel Deaconess Medical Center · Not applicable, Interventional, and Basic science
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.
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.
Beth Israel Deaconess Medical Center is the lead sponsor of 560 studies on the registry; 80 are open to participants now.
Of its 75 completed or terminated interventional studies of FDA-regulated products, 61 (81%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
IV saline with heparin, oral water
Drug: Saline · Dietary Supplement: Water · Drug: Heparin
Intralipid at high dose, with heparin and PO water
Drug: Intralipid · Dietary Supplement: Water · Drug: Heparin
Low dose IV Intralipid with heparin and PO water
Drug: Intralipid · Dietary Supplement: Water · Drug: Heparin
Oral fat load with IV saline
Drug: Saline · Dietary Supplement: Water · Dietary Supplement: oral fat
IV saline at 0.83 mL/kg/hr for six hours
Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours
Also known as: intravenous lipids
Water by mouth
Soybean oil by mouth at 1.25 g/kg x 2 doses
Also known as: soybean oil
Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours
Also known as: anti coated
Change in Circulating Glucagon-like Peptide-1 (GLP-1) Levels
The GLP-1 area under the curve (AUC) was calculated from baseline to six hours
Time frame: Baseline to 6 hours
Change in Circulating Gastric Inhibitory Polypeptide (GIP) Levels
The GIP AUC fwas calculated from baseline to six hours
Time frame: Baseline to 6 hours
Change in Circulating Ghrelin Levels
The Ghrelin AUC was calculated from baseline to six hours
Time frame: Baseline to 6 hours
Change in Circulating Peptide Tyrosine Tyrosine (PYY) Levels
The PYY AUC was calculated from baseline to six hours
Time frame: Baseline to 6 hours
Change in Circulating Glucose Levels
The Glucose AUC was calculated from baseline to six hours
Time frame: Baseline to 6 hours
Change in Circulating Insulin Levels
The Insulin AUC was calculated from baseline to six hours
Time frame: Baseline to 6 hours
Change in Circulating Leptin Levels
The Leptin AUC was calculated from baseline to six hours
Time frame: Baseline to 6 hours
Change in Circulating Adiponectin Levels
The Adiponectin AUC was calculated from baseline to six hours
Time frame: Baseline to 6 hours
Phosphorylation of STAT3 Pathways Downstream of Leptin After Lipid Administration
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
| Milestone | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Started | 9 | 6 | 5 | 6 |
| Completed | 9 | 6 | 5 | 6 |
| Not completed | 0 | 0 | 0 | 0 |
The GLP-1 area under the curve (AUC) was calculated from baseline to six hours
| pM*min | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Change in Circulating Glucagon-like Peptide-1 (GLP-1) Levels | 7147 ± 3547 | 11725 ± 4799 | 11898 ± 9996 | 28060 ± 8414 |
The GIP AUC fwas calculated from baseline to six hours
| pM*min/ml | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Change in Circulating Gastric Inhibitory Polypeptide (GIP) Levels | 12894 ± 8803 | 11830 ± 4516 | 19386 ± 16823 | 60559 ± 36610 |
The Ghrelin AUC was calculated from baseline to six hours
| pg*min/ml | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Change in Circulating Ghrelin Levels | 172886 ± 89970 | 129451 ± 46926 | 207863 ± 111684 | 166195 ± 110140 |
The PYY AUC was calculated from baseline to six hours
| pg*min/ml | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Change in Circulating Peptide Tyrosine Tyrosine (PYY) Levels | 90016 ± 25755 | 65131 ± 14914 | 82474 ± 21072 | 144702 ± 27466 |
The Glucose AUC was calculated from baseline to six hours
| mg*min/dl | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Change in Circulating Glucose Levels | 30683 ± 1249 | 28735 ± 1269 | 32566 ± 1531 | 31364 ± 869 |
The Insulin AUC was calculated from baseline to six hours
| mU*min/ml | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Change in Circulating Insulin Levels | 1765 ± 1555 | 2072 ± 970 | 2103 ± 1645 | 3021 ± 1426 |
The Leptin AUC was calculated from baseline to six hours
| ng*min/ml | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Change in Circulating Leptin Levels | 2050 ± 2233 | 3639 ± 4470 | 5439 ± 4671 | 4973 ± 5313 |
The Adiponectin AUC was calculated from baseline to six hours
| ng*min/ml | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat |
|---|---|---|---|---|
| Change in Circulating Adiponectin Levels | 1546442 ± 500930 | 2273306 ± 1068651 | 1778846 ± 857433 | 1970601 ± 961699 |
Intracellular signaling mechanisms downstream of leptin (particularly the STAT3 pathway) in response to lipid administration as represented by phosphorylation (pSTAT3).
No measurements were reported for this outcome.
Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | — | 0/9 (0%) | 0/9 (0%) |
| High Dose Fat Solution | — | 0/6 (0%) | 0/6 (0%) |
| Low Dose Fat Solution | — | 0/5 (0%) | 0/5 (0%) |
| Oral Fat | — | 0/6 (0%) | 0/6 (0%) |
| Age, Customized(years) | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat | Total |
|---|---|---|---|---|---|
| Median | 35.3 (25.0 to 47.6) | 29.1 (24.2 to 38.7) | 48.6 (44.4 to 54.9) | 27.6 (24.2 to 46.9) | 35.2 (29.5 to 47.0) |
| Sex: Female, Male(Participants) | Placebo | High Dose Fat Solution | Low Dose Fat Solution | Oral Fat | Total |
|---|---|---|---|---|---|
| Female | 2 | 1 | 1 | 3 | 7 |
| Male | 7 | 5 | 4 | 3 | 19 |
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Beth Israel Deaconess Medical Center