- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02321111
The Role of TLR4 on Lipid-induced Insulin Resistance (Eritoran1)
September 16, 2019 updated by: The University of Texas Health Science Center at San Antonio
The Role of TLR4 on Lipid-Induced Insulin Resistance
The purpose of this study is to determine whether pharmacologic inhibition of Toll-like receptor 4 (TLR4) with eritoran for injection (E5564) prevents lipid-induced insulin resistance in lean, normal glucose tolerant (NGT) subjects.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
E5564 = Eritoran
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Texas
-
San Antonio, Texas, United States, 78229
- Audie L. Murphy VA Hospital, STVHCS
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Subjects capable of giving informed consent.
- lean (BMI <26 kg/m2)
- normal glucose-tolerant subjects (completers) without a family history of Type 2 diabetes mellitus (DM)
- Both genders. (50% males)
- Age = 18-65 years. Older subjects are excluded because aging is a pro-inflammatory state.
- All ethnic groups
- Premenopausal women in the follicular phase, non-lactating, and with a negative pregnancy test. Postmenopausal women on stable dose of or not exposed to hormone replacement for >=6 months.
- Lab: Hematocrit >=34%, serum creatinine <=1.4 mg/dL, normal electrolytes, urinalysis, and coagulation tests. Liver function tests up to 2x normal range.
- Stable body weight (+/-1%) for >=3 months.
- One or less sessions of strenuous exercise/wk for last 6 months.
Exclusion Criteria:
- Presence of diabetes or impaired glucose tolerance based on ADA criteria;
- Current treatment with drugs known to affect glucose and lipid homeostasis. Subjects on a stable dose of statin (>3months) are eligible.
- Non-steroidal anti-inflammatory drugs or systemic steroid use for more than 1 week within 3 months.
- Current treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and clopidogrel will be permitted if these can be held for seven days prior to the biopsies.
- History of heart disease (New York Heart Classification greater than class II; more than non-specific ST-T wave changes on the ECG), peripheral vascular disease, pulmonary disease, smokers.
- Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg).
- Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and psychiatric disease.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: D5W (5% Dextrose in water) + Saline
IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours plus Saline infusion at a rate of 30 mL/hour
|
D5W = 5% Dextrose Water Vehicle
Other Names:
|
ACTIVE_COMPARATOR: D5W (5% Dextrose in water) + Intralipid
IV Administration of 5% Dextrose in water /D5W (vehicle) 12 mg plus Intralipid infusion at a rate of 30 ml/hour
|
D5W = 5% Dextrose Water Vehicle
Other Names:
|
ACTIVE_COMPARATOR: Eritoran + Intralipid
IV administration of Eritoran 12 mg every 12 hours plus Intralipid infusion at a rate of 30 ml/hour
|
Eritoran = E5564 Eritoran is a pharmacologic inhibitor of TLR4.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of Eritoran on Muscle Insulin Sensitivity
Time Frame: 72 hours
|
Muscle insulin sensitivity = muscle insulin sensitivity is determined by euglycemic hyperinsulinemic clamp procedure.
M value (mg glucose / kg of body weight / minute) calculated from the clamp is measured.
Higher M value indicates better insulin sensitivity.
There is no established reference range.
|
72 hours
|
Effect of Eritoran on Hepatic Insulin Sensitivity
Time Frame: 72 hours
|
Hepatic insulin sensitivity = is determined by euglycemic hyperinsulinemic clamp procedure.
Endogenous glucose production or EGP (mg/kg/min) calculated from the clamp is measured.
Lower EGP indicates better hepatic insulin sensitivity.
There is no established reference range.
|
72 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of Eritoran on Intramyocellular Diacylglycerol and Ceramide Content
Time Frame: 72 hours
|
Intramyocellular diacylglycerol and ceramide content are determined by mass spectrometry.
Higher levels have been associated with diabetes.
|
72 hours
|
Effect of Eritoran on TLR4 Expression on Peripheral Blood Monocytes
Time Frame: 72 hours
|
TLR4 expression on the peripheral blood monocytes is determined by flow cytometry using arbitrary units.
Higher TLR4 expression indicates higher inflammatory response.
There is no reference range.
|
72 hours
|
Effect of Eritoran on Plasma Cytokine Concentration
Time Frame: 72 hours
|
TNF-alpha levels (tumor necrosis factor-alpha) are determined by ELISA.
Higher level indicates higher inflammatory response.
There is no established reference range.
|
72 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2015
Primary Completion (ACTUAL)
September 1, 2018
Study Completion (ACTUAL)
September 1, 2018
Study Registration Dates
First Submitted
October 29, 2014
First Submitted That Met QC Criteria
December 19, 2014
First Posted (ESTIMATE)
December 22, 2014
Study Record Updates
Last Update Posted (ACTUAL)
October 8, 2019
Last Update Submitted That Met QC Criteria
September 16, 2019
Last Verified
September 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HSC20140497H
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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