Insulin SensitivityPhase 2Eritoran2NCT02267317
The Effect of TLR4 Inhibition in Obese and Type 2 Diabetic Subjects
A Phase 2 study testing Eritoran and D5W in people with Insulin Sensitivity, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Sensitivity
- What is being tested?
- Eritoran and D5W
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Sep 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Audie L. Murphy VA Hospital, STVHCS
San Antonio, Texas, 78229
About this study
Official title: Phase 2 Study of The Role of Pharmacologic Inhibition of TLR4 With E5564 on Glucose Metabolism in Insulin Resistant Subjects.
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.
Read the detailed description
E5564 = Eritoran
- Conditions
- Insulin Sensitivity
- Being tested
- Eritoran, D5W
- Keywords
- Insulin signaling and glucose disposal in muscle, Hepatic insulin sensitivity, TLR4 signaling and inflammatory gene expression, Plasma cytokine concentration, Intramyocellular diacylglycerol and ceramide content
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EritoranDrug
Also called E5564
Pharmacologic inhibitor of TLR4 receptors.
D5WDrug
Also called Placebo, Vehicle
5% Dextrose Water = Vehicle
| Study group | Role | What they receive |
|---|---|---|
| Obese Group-D5W | Active comparator | Obese subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours Receives: Drug: D5W |
| Obese Group - Eritoran | Active comparator | Obese subjects receive IV administration of Eritoran 12 mg every 12 hours Receives: 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 Receives: Drug: D5W |
| Diabetes (T2DM) Group - Eritoran | Active comparator | T2DM subjects receive IV administration of Eritoran 12 mg every 12 hours Receives: Drug: Eritoran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 72 hours
Secondary outcomes (5)
Effect of Eritoran on TLR4 Expression in Muscle Tissue
TLR4 expression in muscle tissue is determined by RNAseq using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range.
Measured: 72 hours
Effect of Eritoran on TLR4 Expresison in Adipose Tissue
TLR4 expression in the adipose tissue is determined by RNAseq using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range.
Measured: 72 hours
Effect of Eritoran on TLR4 Expression in Peripheral Blood Monocytes
TLR4 expression in the peripheral blood monocytes is determined by flow cytometry using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range.
Measured: 72 hours
Effect of Eritoran on Plasma TNF-alpha (Tumor Necrosis Factor-alpha) Concentration
TNF-alpha levels are determined by ELISA. Higher level indicates higher inflammatory response. There is no established reference range.
Measured: 72 hours
Effect of Eritoran on Intramyocellular Diacylglycerol and Ceramide Content
Intramyocellular diacylglycerol and ceramide content are determined by mass spectrometry. Higher levels have been associated with diabetes.
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2014 (estimated)
- Study startJan 2015
- Primary completionSep 2018
- Study completionSep 2018
Why it stopped: Study drug expired
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Insulin SensitivityStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas Musi, MD, Principal investigator, Audie L. Murphy VA Hospital, STVHCS San Antonio, Texas, United States 78229
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02267317
- Sponsor's protocol ID
- HSC20140498H
- Acronym
- Eritoran2
- Status last verified
- Sep 2018
- First submitted
- 26 Sep 2014
- Last updated
- 4 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 36066991
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of The Role of Pharmacologic Inhibition of TLR4 With E5564 on Glucose Metabolism in Insulin Resistant Subjects.
- ClinicalTrials.gov ID
- NCT02267317
- Acronym / sponsor ID
- Eritoran2 / HSC20140498H
- Conditions
- Insulin Sensitivity
- Keywords
- Insulin signaling and glucose disposal in muscle, Hepatic insulin sensitivity, TLR4 signaling and inflammatory gene expression, Plasma cytokine concentration, Intramyocellular diacylglycerol and ceramide content
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study drug expired
- Enrolment
- 15 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 17 Oct 2014 (estimated)
- Results
- Posted 4 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
E5564 = Eritoran
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Obese Group-D5W | Active comparator | Drug: D5WObese subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours |
| Obese Group - Eritoran | Active comparator | Drug: EritoranObese subjects receive IV administration of Eritoran 12 mg every 12 hours |
| Diabetes (T2DM) Group - D5W | Active comparator | Drug: D5WT2DM subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours |
| Diabetes (T2DM) Group - Eritoran | Active comparator | Drug: EritoranT2DM subjects receive IV administration of Eritoran 12 mg every 12 hours |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EritoranAlso: E5564Pharmacologic inhibitor of TLR4 receptors. | Drug | Diabetes (T2DM) Group - Eritoran, Obese Group - Eritoran |
| D5WAlso: Placebo, Vehicle5% Dextrose Water = Vehicle | Drug | Diabetes (T2DM) Group - D5W, Obese Group-D5W |
Primary outcome
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.
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.
5 secondary outcomes
Effect of Eritoran on TLR4 Expression in Muscle Tissue
Time frame: 72 hours
Effect of Eritoran on TLR4 Expresison in Adipose Tissue
Time frame: 72 hours
Effect of Eritoran on TLR4 Expression in Peripheral Blood Monocytes
Time frame: 72 hours
Effect of Eritoran on Plasma TNF-alpha (Tumor Necrosis Factor-alpha) Concentration
Time frame: 72 hours
Effect of Eritoran on Intramyocellular Diacylglycerol and Ceramide Content
Time frame: 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36066991Liang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas Musi, MD principal investigator
Audie L. Murphy VA Hospital, STVHCS San Antonio, Texas, United States 78229
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eritoran and D5W in people with Insulin Sensitivity, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of Eritoran on Muscle Insulin Sensitivity (time frame: 72 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02267317, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2020.