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

NCT01740817 | Completed Results

• 2 other identifiers: HSC20080015H5R01DK080157
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Conditions

Diabetes; Obesity

Keywords

diabetes; obesity; inflammation

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• TLR4 Messenger Ribonucleic Acid (mRNA) in Muscle

  48 hr following lipid/saline infusion, pre-clamp

• Extracellular Signal-regulated Kinase (ERK) Phosphorylation in Muscle

  48 hr following lipid or saline infusion, pre-clamp

Study Arms (2)

Intralipid 20%, then saline

EXPERIMENTAL

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%; Drug: Saline

Saline, then Intralipid

EXPERIMENTAL

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%; Drug: Saline

Interventions

Intralipid 20% DRUG

30 ml/h for 48 h

Also known as: Liposyn

Intralipid 20%, then saline; Saline, then Intralipid

Saline DRUG

30 ml/h for 48 h

Also known as: sodium chloride injection

Intralipid 20%, then saline; Saline, then Intralipid

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• 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.
• Subjects whose body weight has been stable (within 2%) for at least three months.

You may not qualify if:

• Subjects with impaired glucose tolerance based on American Diabetes Association criteria.
• 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.
• 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.
• 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.
• Subjects who smoke.
• Subjects who engage in a regular exercise program (zero or one exercise sessions per week are allowed).
• Any subject who has donated blood in the previous two months.
• Any subject with a hematocrit of less than 35.
• Subjects who are claustrophobic.
• Women taking oral contraceptives.
• alcohol consumption greater than 30 grams daily.
• baseline plasma triglyceride levels over 200 mg/dl

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Audie L. Murphy VA Hospital

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Hussey SE, Lum H, Alvarez A, Cipriani Y, Garduno-Garcia J, Anaya L, Dube J, Musi N. A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle. Diabetologia. 2014 Mar;57(3):582-91. doi: 10.1007/s00125-013-3111-x. Epub 2013 Dec 14.

  PMID: 24337154 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Obesity; Inflammation

Interventions

safflower oil, soybean oil, lecithin emulsion; Sodium Chloride

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Nicolas Musi
• Organization: University of Texas Health Science Center at San Antonio

musi@uthscsa.edu

200-562-6152

Study Officials

• Nicolas Musi, MD

  Univerisity of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Diabetes Division

Study Record Dates

• First Submitted: November 26, 2012
• First Posted: December 4, 2012
• Study Start: January 1, 2008
• Primary Completion: December 1, 2013
• Study Completion: September 1, 2015
• Last Updated: January 25, 2016
• Results First Posted: January 25, 2016

Record last verified: 2015-12

Locations

US (1)