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A Study to Evaluate the Effect of Lipid Infusion on Toll Like Receptor 4 (TLR4) Signaling

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01740817
Recruitment Status : Completed
First Posted : December 4, 2012
Results First Posted : January 25, 2016
Last Update Posted : January 25, 2016
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Nicolas Musi, MD, The University of Texas Health Science Center at San Antonio

Brief Summary:
The purpose of this study is to determine whether a lipid infusion can up-regulate toll-like receptor 4 (TLR4) signaling in human subjects

Condition or disease Intervention/treatment Phase
Diabetes Obesity Drug: Intralipid 20% Drug: Saline Not Applicable

Detailed Description:
The investigators plan to examine the effect of a lipid infusion on TLR4 expression and insulin sensitivity. A group of 30 subjects aged 18-60 years old, lean (BMI < 26 kg/m2) normal glucose tolerant subjects without a family history of type 2 diabetes will receive a lipid or saline infusion. The subjects will be randomly assigned to first receive either a 48 hour long lipid or saline infusion. Approximately 4-6 weeks later subjects will return to undergo another study (if, in the first study they received lipid, on the second study they will receive saline, and vice versa). A near-equal number of women and men will be included in each group.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Randomized, Crossover Study to Evaluate the Effect of Lipid Infusion on TLR4 Signaling and Insulin Resistance in Human Muscle
Study Start Date : January 2008
Actual Primary Completion Date : December 2013
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intralipid 20%, then saline
Participants first received lipid infusion of 30ml/h x48h. After a washout period of 4-6 weeks, they then received saline infusion of 30ml/h x48h.
Drug: Intralipid 20%
30 ml/h for 48 h
Other Name: Liposyn

Drug: Saline
30 ml/h for 48 h
Other Name: sodium chloride injection

Experimental: Saline, then Intralipid
Participants first received saline infusion of 30ml/h x48h. After a washout period of 4-6 weeks, they then received lipid infusion of 30ml/h x48h.
Drug: Intralipid 20%
30 ml/h for 48 h
Other Name: Liposyn

Drug: Saline
30 ml/h for 48 h
Other Name: sodium chloride injection




Primary Outcome Measures :
  1. Muscle Insulin Sensitivity-M Value [ Time Frame: 48 hr after lipid/saline infusion ]

    Forty eight hrs after lipid or saline infusion, muscle insulin sensitivity will be measured by insulin clamp. The results are compared to determine whether lipid infusion reduces muscle insulin sensitivity compared to saline infusion..

    The M value is defined as the exogenous glucose infusion rate at steady state (i.e, when the exogenous glucose infusion rate is equal to the rate of whole body glucose disposal).



Secondary Outcome Measures :
  1. TLR4 Messenger Ribonucleic Acid (mRNA) in Muscle [ Time Frame: 48 hr following lipid/saline infusion, pre-clamp ]

    Forty eight hrs after lipid or saline infusion, muscle TLR4 mRNA levels will be measured by RT-PCR. The results are compared to determine whether lipid infusion increases muscle TLR4 mRNA expression compared to saline infusion.

    Saline mean was used to normalize the data for both arms.


  2. Extracellular Signal-regulated Kinase (ERK) Phosphorylation in Muscle [ Time Frame: 48 hr following lipid or saline infusion, pre-clamp ]
    Forty eight hrs after lipid or saline infusion, muscle ERK phosphorylation will be measured by western blot. The results are compared to determine whether lipid infusion increases muscle ERK phosphorylation compared to saline infusion. Saline mean was used to normalize the data for both arms.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Subjects must have the following laboratory values: Hematocrit ≥ 35%, serum creatinine ≤ 1.5 mg/dl, aspartate aminotransferase (AST) < 2 X upper limit of normal, Alanine aminotransferase (ALT) < 2 X upper limit of normal, alkaline phosphatase < 2 X upper limit of normal, normal urinalysis [no glucose, trace protein, trace ketones, lipase < 50 IU/L, no bacteria, up to 1-3 white blood cells (WBC) and red blood cells (RBC) per hpf], and normal platelets, prothrombin time (PT) and partial thromboplastin time (PTT).
  2. Female subjects must be non-lactating. Female patients are eligible only if they have a negative pregnancy test throughout the study period (or postmenopausal). Postmenopausal women taking hormone replacement will be included if they have been on a stable dose for ≥6 months.
  3. Subjects whose body weight has been stable (within 2%) for at least three months.

Exclusion Criteria:

  1. Subjects with impaired glucose tolerance based on American Diabetes Association criteria.
  2. Subjects taking drugs known to affect glucose and lipid homeostasis will be excluded. Statins will be permitted if the subject has been on a stable dose for at least three months. Subjects who have taken for more than a week non-steroidal anti inflammatory drugs (NSAIDS) within two months or systemic steroids, anabolic steroids, growth hormone or immunosuppressants within 12 months will be excluded. Subjects taking low-dose (81 mg/day or less) aspirin will be allowed.
  3. Patients with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
  4. Recent systemic or pulmonary embolus, impaired renal function, poorly controlled blood pressure (systolic BP>170, diastolic BP>95), resting heart rate >100, electrolyte abnormalities, neuromuscular or musculoskeletal disease.
  5. Subjects who smoke.
  6. Subjects who engage in a regular exercise program (zero or one exercise sessions per week are allowed).
  7. Any subject who has donated blood in the previous two months.
  8. Any subject with a hematocrit of less than 35.
  9. Subjects who are claustrophobic.
  10. Women taking oral contraceptives.
  11. alcohol consumption greater than 30 grams daily.
  12. baseline plasma triglyceride levels over 200 mg/dl

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01740817


Locations
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United States, Texas
Audie L. Murphy VA Hospital
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Nicolas Musi, MD Univerisity of Texas Health Science Center at San Antonio
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Nicolas Musi, MD, Professor Diabetes Division, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01740817    
Other Study ID Numbers: HSC20080015H
5R01DK080157 ( U.S. NIH Grant/Contract )
First Posted: December 4, 2012    Key Record Dates
Results First Posted: January 25, 2016
Last Update Posted: January 25, 2016
Last Verified: December 2015
Keywords provided by Nicolas Musi, MD, The University of Texas Health Science Center at San Antonio:
diabetes
obesity
inflammation
Additional relevant MeSH terms:
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Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Soybean oil, phospholipid emulsion
Fat Emulsions, Intravenous
Parenteral Nutrition Solutions
Pharmaceutical Solutions