NCT02267317

Brief Summary

To determine whether pharmacologic inhibition of Toll-like receptor 4 (TLR4) with eritoran for injection (E5564) will reduce inflammation and improve glucose metabolism in insulin resistant (obese and T2DM) subjects.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2015

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 26, 2014

Completed
21 days until next milestone

First Posted

Study publicly available on registry

October 17, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

January 1, 2015

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2018

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

March 4, 2020

Completed
Last Updated

March 4, 2020

Status Verified

September 1, 2018

Enrollment Period

3.7 years

First QC Date

September 26, 2014

Results QC Date

January 22, 2020

Last Update Submit

February 24, 2020

Conditions

Insulin Sensitivity

Keywords

Insulin signaling and glucose disposal in muscleHepatic insulin sensitivityTLR4 signaling and inflammatory gene expressionPlasma cytokine concentrationIntramyocellular diacylglycerol and ceramide content

Outcome Measures

Primary Outcomes (2)

  • Effect of Eritoran on Muscle Insulin Sensitivity

    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

    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 Outcomes (5)

  • Effect of Eritoran on TLR4 Expression in Muscle Tissue

    72 hours

  • Effect of Eritoran on TLR4 Expresison in Adipose Tissue

    72 hours

  • Effect of Eritoran on TLR4 Expression in Peripheral Blood Monocytes

    72 hours

  • Effect of Eritoran on Plasma TNF-alpha (Tumor Necrosis Factor-alpha) Concentration

    72 hours

  • Effect of Eritoran on Intramyocellular Diacylglycerol and Ceramide Content

    72 hours

Study Arms (4)

Obese Group-D5W

ACTIVE COMPARATOR

Obese subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours

Drug: D5W

Obese Group - Eritoran

ACTIVE COMPARATOR

Obese subjects receive IV administration of Eritoran 12 mg every 12 hours

Drug: Eritoran

Diabetes (T2DM) Group - D5W

ACTIVE COMPARATOR

T2DM subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours

Drug: D5W

Diabetes (T2DM) Group - Eritoran

ACTIVE COMPARATOR

T2DM subjects receive IV administration of Eritoran 12 mg every 12 hours

Drug: Eritoran

Interventions

EritoranDRUG

Pharmacologic inhibitor of TLR4 receptors.

Also known as: E5564
Diabetes (T2DM) Group - EritoranObese Group - Eritoran
D5WDRUG

5% Dextrose Water = Vehicle

Also known as: Placebo, Vehicle
Diabetes (T2DM) Group - D5WObese Group-D5W

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subjects capable of giving informed consent.
  • lean (BMI \<26 kg/m2) with normal glucose-tolerant subjects without a family history of type 2 DM
  • obese (BMI 30-37 kg/m2) with normal glucose-tolerant subjects
  • Type 2 DM subjects base on ADA criteria, who have HbA1c \<8.5% and control with diet or sulfonylureas.
  • 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.

You may not qualify if:

  • Current treatment with drugs known to affect glucose and lipid homeostasis. Subjects on a stable dose of statin (\>3 months) 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Audie L. Murphy VA Hospital, STVHCS

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

  • Liang H, Sathavarodom N, Colmenares C, Gelfond J, Espinoza SE, Ganapathy V, Musi N. Effect of acute TLR4 inhibition on insulin resistance in humans. J Clin Invest. 2022 Nov 1;132(21):e162291. doi: 10.1172/JCI162291.

    PMID: 36066991DERIVED

MeSH Terms

Conditions

Insulin Resistance

Interventions

eritoranE5564

Condition Hierarchy (Ancestors)

HyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Results Point of Contact

Title
Hanyu Liang
Organization
University of Texas Health San Antonio
liangh0@uthscsa.edu
210-617-5300

Study Officials

  • Nicolas Musi, MD

    Audie L. Murphy VA Hospital, STVHCS San Antonio, Texas, United States 78229

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Participant, Care Provider, Investigator, Outcomes Assessor
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 26, 2014

First Posted

October 17, 2014

Study Start

January 1, 2015

Primary Completion

September 1, 2018

Study Completion

September 1, 2018

Last Updated

March 4, 2020

Results First Posted

March 4, 2020

Record last verified: 2018-09

Locations

US(1)