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Effect of Increased Free Fatty Acids on Leptin Function

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Beth Israel Deaconess Medical Center
Sponsor:
Information provided by (Responsible Party):
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01520454
First received: January 4, 2012
Last updated: February 19, 2013
Last verified: February 2013

January 4, 2012
February 19, 2013
November 2011
December 2013   (final data collection date for primary outcome measure)
Change in intracellular messengers of leptin signaling [ Time Frame: Baseline to 6 hours ] [ Designated as safety issue: No ]
We will look at the change from baseline to +6 hours of a range of intracellular messengers associated with leptin signaling, most prominently STAT3/pSTAT3 ratio.
Change in intracellular messengers of leptin signaling [ Time Frame: Baseline to 6 hours ] [ Designated as safety issue: No ]
We will look at the change from baseline to +6 hours of a range of intracellular messengers associated with leptin signaliong, most prominently STAT3/pSTAT3 ratio.
Complete list of historical versions of study NCT01520454 on ClinicalTrials.gov Archive Site
  • Change in circulating levels of gut hormones (GLP-1, GIP, ghrelin, PYY) [ Time Frame: Baseline to 6 hours ] [ Designated as safety issue: No ]
    We will assess the change from baseline to six hours in these gut-secreted hormones and compare between different intervention groups.
  • Change in circulating hormone levels [ Time Frame: Baseline to 6 hours ] [ Designated as safety issue: No ]
    We will assess the change from baseline to 6 hours in a range of standard hormones including insulin, glucose, thyroid hormones, growth hormones, etc. as well as leptin and other adipokines. We will compare the different interventional groups.
Same as current
Not Provided
Not Provided
 
Effect of Increased Free Fatty Acids on Leptin Function
Lipotoxicity and Leptin Signaling

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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
  • Obesity
  • Leptin Resistance
  • Drug: Saline
    IV saline at 0.83 mL/kg/hr for six hours
  • Drug: Intralipid
    Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours
  • Dietary Supplement: Water
    Water by mouth
  • Dietary Supplement: Soybean oil
    Soybean oil by mouth at 1.25 g/kg x 2 doses
  • Drug: Heparin
    Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours
  • Placebo Comparator: Placebo
    IV saline with heparin, oral water
    Interventions:
    • Drug: Saline
    • Dietary Supplement: Water
    • Drug: Heparin
  • Experimental: High dose fat solution
    Intralipid at high dose, with heparin and PO water
    Interventions:
    • Drug: Intralipid
    • Dietary Supplement: Water
    • Drug: Heparin
  • Experimental: Low dose fat solution
    Low dose IV Intralipid with heparin and PO water
    Interventions:
    • Drug: Intralipid
    • Dietary Supplement: Water
    • Drug: Heparin
  • Experimental: Oral fat
    Oral fat load with IV saline
    Interventions:
    • Drug: Saline
    • Dietary Supplement: Water
    • Dietary Supplement: Soybean oil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
December 2013
December 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
Yes
Contact: Christos S Mantzoros, MD, DSc 617-667-1656 cmantzor@bidmc.harvard.edu
Contact: Lesya Zaichekno, BA 617-667-8630 lzaichen@bidmc.harvard.edu
United States
 
NCT01520454
2009P-000370
No
Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center
Not Provided
Principal Investigator: Christos S Mantzoros, MD, DSc Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP