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
  Purpose

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.


Condition Intervention
Obesity
Leptin Resistance
Drug: Saline
Drug: Intralipid
Dietary Supplement: Water
Dietary Supplement: Soybean oil
Drug: Heparin

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Lipotoxicity and Leptin Signaling

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 50
Study Start Date: November 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 PTT, for 5.5 hours
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
Dietary Supplement: Water
Water by mouth
Drug: Heparin
Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours
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
Dietary Supplement: Water
Water by mouth
Drug: Heparin
Heparin bolus of 1000 units followed by 800 u/hr, adjust per PTT, for 5.5 hours
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: Soybean oil
Soybean oil by mouth at 1.25 g/kg x 2 doses

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520454

Contacts
Contact: Christos S Mantzoros, MD, DSc 617-667-1656 cmantzor@bidmc.harvard.edu
Contact: Lesya Zaichekno, BA 617-667-8630 lzaichen@bidmc.harvard.edu

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
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
  More Information

Additional Information:
No publications provided

Responsible Party: Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01520454     History of Changes
Other Study ID Numbers: 2009P-000370
Study First Received: January 4, 2012
Last Updated: February 19, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
Leptin resistance
Free fatty acids
Lipotoxicity

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Calcium heparin
Heparin
Soybean oil, phospholipid emulsion
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Fat Emulsions, Intravenous
Parenteral Nutrition Solutions
Pharmaceutical Solutions

ClinicalTrials.gov processed this record on September 11, 2014