DiabetesNCT01740817
A Study to Evaluate the Effect of Lipid Infusion on Toll Like Receptor 4 (TLR4) Signaling
A study testing Intralipid 20% and Saline in people with Diabetes and Obesity, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
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 Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- What is being tested?
- Intralipid 20% and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Sep 2015
- Phase
- Interventional
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Audie L. Murphy VA Hospital
San Antonio, Texas, 78229
About this study
Official title: A Randomized, Crossover Study to Evaluate the Effect of Lipid Infusion on TLR4 Signaling and Insulin Resistance in Human Muscle
The purpose of this study is to determine whether a lipid infusion can up-regulate toll-like receptor 4 (TLR4) signaling in human subjects
Read the detailed 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.
- Being tested
- Intralipid 20%, Saline
- Keywords
- diabetes, obesity, inflammation
- Medical subject headings
- Diabetes Mellitus, Obesity, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intralipid 20%Drug
Also called Liposyn
30 ml/h for 48 h
SalineDrug
Also called sodium chloride injection
30 ml/h for 48 h
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Intralipid 20%; Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 48 hr after lipid/saline infusion
Secondary outcomes (2)
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.
Measured: 48 hr following lipid/saline infusion, pre-clamp
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.
Measured: 48 hr following lipid or saline infusion, pre-clamp
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2012 (estimated)
- Study startJan 2008
- Primary completionDec 2013
- Study completionSep 2015
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 DiabetesStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicolas Musi, MD, The University of Texas Health Science Center at San Antonio
- Investigators
- Nicolas Musi, MD, Principal investigator, Univerisity of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01740817
- Sponsor's protocol ID
- HSC20080015H
- Other IDs
- 5R01DK080157
- Status last verified
- Dec 2015
- First submitted
- 26 Nov 2012
- Last updated
- 25 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 24337154
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Crossover Study to Evaluate the Effect of Lipid Infusion on TLR4 Signaling and Insulin Resistance in Human Muscle
- ClinicalTrials.gov ID
- NCT01740817
- Acronym / sponsor ID
- HSC20080015H
- Keywords
- diabetes, obesity, inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jan 2008
- Primary completion
- Dec 2013 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 4 Dec 2012 (estimated)
- Results
- Posted 25 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether a lipid infusion can up-regulate toll-like receptor 4 (TLR4) signaling in human subjects
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intralipid 20%, then saline | Experimental | Drug: Intralipid 20%, Drug: SalineParticipants 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. |
| Saline, then Intralipid | Experimental | Drug: Intralipid 20%, Drug: SalineParticipants 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
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 |
|---|---|---|
| Intralipid 20%Also: Liposyn30 ml/h for 48 h | Drug | Intralipid 20%, then saline, Saline, then Intralipid |
| SalineAlso: sodium chloride injection30 ml/h for 48 h | Drug | Intralipid 20%, then saline, Saline, then Intralipid |
Primary outcome
Muscle Insulin Sensitivity-M Value
Time frame: 48 hr after lipid/saline infusion
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).
2 secondary outcomes
TLR4 Messenger Ribonucleic Acid (mRNA) in Muscle
Time frame: 48 hr following lipid/saline infusion, pre-clamp
Extracellular Signal-regulated Kinase (ERK) Phosphorylation in Muscle
Time frame: 48 hr following lipid or saline infusion, pre-clamp
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24337154Hussey 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.
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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
Univerisity of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intralipid 20% and Saline in people with Diabetes and Obesity, 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 3 inclusion and 12 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: finished, as of the sponsor's last update on 25 Jan 2016. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jan 2016). 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?
Muscle Insulin Sensitivity-M Value (time frame: 48 hr after lipid/saline infusion). 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 NCT01740817, 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 25 Jan 2016.