Overview

This trial is active, not recruiting.

Conditions obesity, leptin resistance
Treatments saline, intralipid, water, soybean oil, heparin
Sponsor Beth Israel Deaconess Medical Center
Start date November 2011
End date December 2013
Trial size 44 participants
Trial identifier NCT01520454, 2009P-000370

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.

It has been shown that obese people also have higher levels of free fatty acids in the blood when compared with lean people, and that this may cause impaired effect of insulin. The investigators believe that elevated free fatty acids may also affect leptin function. In this study, the investigators are increasing the levels of free fatty acids in healthy volunteers and looking for effects on leptin function before and after.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose basic science
Arm
(Placebo Comparator)
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
(Experimental)
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
(Experimental)
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
(Experimental)
Oral fat load with IV saline
saline
IV saline at 0.83 mL/kg/hr for six hours
water
Water by mouth
soybean oil
Soybean oil by mouth at 1.25 g/kg x 2 doses

Primary Outcomes

Measure
Change in intracellular messengers of leptin signaling
time frame: Baseline to 6 hours

Secondary Outcomes

Measure
Change in circulating levels of gut hormones (GLP-1, GIP, ghrelin, PYY)
time frame: Baseline to 6 hours
Change in circulating hormone levels
time frame: Baseline to 6 hours

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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.

Additional Information

Official title Lipotoxicity and Leptin Signaling
Principal investigator Christos S Mantzoros, MD, DSc
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by Beth Israel Deaconess Medical Center.