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

Obesity Clinical Trial

Official title:

A Randomized, Crossover Study to Evaluate the Effect of Lipid Infusion on TLR4 Signaling and Insulin Resistance in Human Muscle

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01740817
• Other study ID #: HSC20080015H
• Secondary ID: 5R01DK080157
• Status: Completed
• Phase: N/A
• First received: November 26, 2012
• Last updated: December 18, 2015
• Start date: January 2008
• Est. completion date: September 2015

Study information

• Verified date: December 2015
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 2015
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes
• Obesity

Intervention

Drug:
• Intralipid 20%
30 ml/h for 48 h
• Saline
30 ml/h for 48 h

Locations

Country	Name	City	State
United States	Audie L. Murphy VA Hospital	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Muscle Insulin Sensitivity-M Value	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).	48 hr after lipid/saline infusion	No
Secondary	TLR4 Messenger Ribonucleic Acid (mRNA) in Muscle	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.	48 hr following lipid/saline infusion, pre-clamp	No
Secondary	Extracellular Signal-regulated Kinase (ERK) Phosphorylation in Muscle	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.	48 hr following lipid or saline infusion, pre-clamp	No