Insulin ResistancePhase 4NCT02403284
The Effect of Liraglutide on Dietary Lipid Induced Insulin Resistance in Humans
A Phase 4 study testing Liraglutide and Sugar Pill in people with Insulin Resistance, run by Phoenix VA Health Care System at 1 site in United States.
Trial summary
In this research study, investigators will test the effects of an approved medication for diabetes,Liraglutide, to reduce insulin resistance that develops from eating a diet high in saturated fats. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- Liraglutide and Sugar Pill
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 97 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to 1 Nov 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 40-75 years old
- Body mass index (BMI) from 22 to 35 kg/m2
- Normal glucose tolerance as determined by fasting blood glucose (< 100 mg/dl) and 75 gm glucose load (2 hr glucose <140 mg/dl)
- Fasting triglyceride levels ≥ 75 mg/dl and <500 mg/dl
Who cannot join
- Type 1 or 2 diabetes mellitus or a hemoglobin A1c value >6.5 mg/dl
- Any diabetes medications in the past month, thiazolidinedione medications in the prior 3 months or prior regular use of insulin
- Lactose intolerance or avoidance of dairy products
- Creatinine > 2.0 mg/dl or other laboratory evidence of active disease, including hepatic enzyme elevation (AST or ALT) > 2.5 x normal and anemia (Hct < 35)
- Known 'Nonalcoholic Fatty Liver Disease'
- Malabsorption of fat or other nutrients, severe lactose intolerance or other significant gastrointestinal or pancreatic problems (including history of acute or chronic pancreatitis).
Show all 16Show fewer
- Recent history of nausea or vomiting
- Acute bacterial or viral illness or evidence of other active infection in the past 4 weeks
- Prior cardiovascular event, stable or unstable angina or other major illness in the past 6 months
- Current regular use of anti-inflammatory medications or antioxidants in excess of a standard daily multi-vitamin, including over- the-counter medications and high dose salicylates (> 1 gm/ day)
- Subjects receiving a lipid lowering medication must be on a stable dose for at least 6 weeks prior to participation.
- Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia 2
- Ethanol consumption more than 4 oz day
- Pregnancy, or lack of appropriate contraceptive use in premenopausal women (extremely rare in our older predominately male population)
- Poorly controlled hypertension, systolic blood pressure (SBP) > 150 or diastolic blood pressure (DBP) > 90 on 2 or more occasions during screening visits. Subjects receiving blood pressure medication will be on a stable dosing for at least 6 weeks prior to participation.
- BMI <22 and >35 kg/m2
Trial locations and contacts
1 site in 1 country.
United States1 site
Carl T. Hayden VA Medical Hospital
Phoenix, Arizona, 85012
About this study
In this research study, investigators will test the effects of an approved medication for diabetes,Liraglutide, to reduce insulin resistance that develops from eating a diet high in saturated fats.
Read the detailed description
The specific aim of this study is to determine the ability of subacute liraglutide administration to protect against dietary lipid induced peripheral insulin resistance in non-diabetic subjects who have normal glucose tolerance. Recent data from our laboratory and others suggest that high fat meals, enriched with saturated fatty acids (SFA) in particular, have a unique and profound ability to induce rapid (in ≤ 24 hr) and profound onset of insulin resistance in humans. This is presumably mediated in part through delivery of lipids and lipid products generated during postprandial lipolysis into non-adipose tissue. This unique model therefore provides an excellent platform to test agents for their ability to inhibit dietary induced insulin resistance. As we and others have demonstrated the ability of GLP-1 receptor agonists to markedly suppress postprandial lipid elevations and to modify lipid metabolism, we hypothesize that liraglutide may be an effective agent to inhibit development of dietary induced insulin resistance.
- Conditions
- Insulin Resistance
- Being tested
- Liraglutide, Sugar Pill
- Keywords
- insulin resistance, lipid metabolism, glucose metabolism, high fat diets
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Also called Victoza
Subcutaneous injection by patient
Sugar PillDrug
Also called Placebo
Subcutaneous injection daily
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Experimental | Liraglutide titration up to 1.8 mg/d over approximately 3 weeks Receives: Drug: Liraglutide |
| Sugar pill | Placebo comparator | matching placebo and titration Receives: Drug: Sugar Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole Body Insulin Sensitivity (insulin suppression test)
An insulin suppression test will be measured before and approximately 3 weeks after each treatment phase. Key time frames for assessing steady state plasma glucose will be between 150 and 180 minutes during the insulin suppression test
Measured: 3 weeks
Secondary outcomes (9)
Postprandial lipid changes (area under the curve difference in triglyceride,total apolipoprotein B100, apolipoprotein B48, and apolipoprotein C3.
The major endpoints will be the area under the curve difference in triglyceride and free fatty acids between treatment arms on test day 1 and 2 following a standard meal. Other postprandial lipids will include total apolipoprotein B100, apolipoprotein B48, and apolipoprotein C3.
Measured: 3 weeks
Postprandial changes in glucose metabolism (total and incremental area under the curve differences in glucose, insulin and glucagon)
total and incremental area under the curve differences in glucose, insulin and glucagon between treatment arms
Measured: 3 weeks
Changes in adipose tissue insulin signaling pathway activation (compare insulin signaling pathway activity (e.g., Akt and insulin receptor phosphorylation)
Adipose tissue biopsy samples will be used to compare insulin signaling pathway activity (e.g., Akt and insulin receptor phosphorylation) in placebo and liraglutide treatment phases.
Measured: 3 weeks
subcutaneous adipose tissue lipid intermediates (e.g., ceramide, diacylglycerol, acylcarnitine concentrations)
Adipose tissue biopsy samples will be used to compare lipid intermediates in placebo and liraglutide treatment phases.
Measured: 3 weeks
skeletal muscle tissue lipid intermediates (e.g., ceramide, diacylglycerol, acylcarnitine concentrations)
skeletal muscle tissue samples will be used to compare lipid intermediates in placebo and liraglutide treatment phases.
Measured: 3 weeks
Adipose tissue inflammation measures (e.g., interleukin (IL)-6, and -8, adiponectin, TNF-alpha, nuclear factor-kappa b, gene and protein expression)
Adipose tissue biopsy samples will be used to compare inflammation measures in placebo and liraglutide treatment phases.
Measured: 3 weeks
Skeletal muscle inflammation measures (e.g., IL-6,8, TNF-alpha, nuclear factor-kappa b gene and protein expression)
skeletal muscle tissue samples will be used to compare inflammation measures in placebo and liraglutide treatment phases
Measured: 3 weeks
Adipose tissue arteriole function (vasodilation measurement)
Adipose tissue biopsy samples will be used to isolate arterioles and measure ex vivo vascular function in placebo and liraglutide treatment phases.
Measured: 3 weeks
Changes in skeletal muscle insulin signaling pathway
skeletal muscle biopsy samples will be used to compare insulin signaling pathway activity (e.g., Akt and insulin receptor phosphorylation) in placebo and liraglutide treatment phases.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2015 (estimated)
- Study startMar 2013
- Primary completion28 Apr 2021
- Study completion1 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- Phoenix VA Health Care System
- Sponsor type
- US federal agency
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Peter D Reaven, MD, Principal investigator, Carl T. Hayden Medical Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02403284
- Sponsor's protocol ID
- 028
- Other IDs
- 1593855
- Status last verified
- Jul 2024
- First submitted
- 3 Nov 2014
- Last updated
- 22 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: Subject to VA regulation.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Liraglutide on Dietary Lipid Induced Insulin Resistance in Humans
- ClinicalTrials.gov ID
- NCT02403284
- Acronym / sponsor ID
- 028
- Conditions
- Insulin Resistance
- Keywords
- insulin resistance, lipid metabolism, glucose metabolism, high fat diets
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- Phoenix VA Health Care SystemUS federal agency
- Collaborators
- Novo Nordisk A/S
- Study start
- Mar 2013
- Primary completion
- 28 Apr 2021 (actual)
- Study completion
- 1 Nov 2023 (actual)
- First posted
- 31 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this research study, investigators will test the effects of an approved medication for diabetes,Liraglutide, to reduce insulin resistance that develops from eating a diet high in saturated fats.
Detailed description
The specific aim of this study is to determine the ability of subacute liraglutide administration to protect against dietary lipid induced peripheral insulin resistance in non-diabetic subjects who have normal glucose tolerance. Recent data from our laboratory and others suggest that high fat meals, enriched with saturated fatty acids (SFA) in particular, have a unique and profound ability to induce rapid (in ≤ 24 hr) and profound onset of insulin resistance in humans. This is presumably mediated in part through delivery of lipids and lipid products generated during postprandial lipolysis into non-adipose tissue. This unique model therefore provides an excellent platform to test agents for their ability to inhibit dietary induced insulin resistance. As we and others have demonstrated the ability of GLP-1 receptor agonists to markedly suppress postprandial lipid elevations and to modify lipid metabolism, we hypothesize that liraglutide may be an effective agent to inhibit development of dietary induced insulin resistance.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Experimental | Drug: LiraglutideLiraglutide titration up to 1.8 mg/d over approximately 3 weeks |
| Sugar pill | Placebo comparator | Drug: Sugar Pillmatching placebo and titration |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 40-75 years old
- Body mass index (BMI) from 22 to 35 kg/m2
- Normal glucose tolerance as determined by fasting blood glucose (< 100 mg/dl) and 75 gm glucose load (2 hr glucose <140 mg/dl)
- Fasting triglyceride levels ≥ 75 mg/dl and <500 mg/dl
Key exclusion criteria (16 listed)
- Type 1 or 2 diabetes mellitus or a hemoglobin A1c value >6.5 mg/dl
- Any diabetes medications in the past month, thiazolidinedione medications in the prior 3 months or prior regular use of insulin
- Lactose intolerance or avoidance of dairy products
- Creatinine > 2.0 mg/dl or other laboratory evidence of active disease, including hepatic enzyme elevation (AST or ALT) > 2.5 x normal and anemia (Hct < 35)
- Known 'Nonalcoholic Fatty Liver Disease'
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 |
|---|---|---|
| LiraglutideAlso: VictozaSubcutaneous injection by patient | Drug | Liraglutide |
| Sugar PillAlso: PlaceboSubcutaneous injection daily | Drug | Sugar pill |
Primary outcome
Whole Body Insulin Sensitivity (insulin suppression test)
Time frame: 3 weeks
An insulin suppression test will be measured before and approximately 3 weeks after each treatment phase. Key time frames for assessing steady state plasma glucose will be between 150 and 180 minutes during the insulin suppression test
9 secondary outcomes
Postprandial lipid changes (area under the curve difference in triglyceride,total apolipoprotein B100, apolipoprotein B48, and apolipoprotein C3.
Time frame: 3 weeks
Postprandial changes in glucose metabolism (total and incremental area under the curve differences in glucose, insulin and glucagon)
Time frame: 3 weeks
Changes in adipose tissue insulin signaling pathway activation (compare insulin signaling pathway activity (e.g., Akt and insulin receptor phosphorylation)
Time frame: 3 weeks
subcutaneous adipose tissue lipid intermediates (e.g., ceramide, diacylglycerol, acylcarnitine concentrations)
Time frame: 3 weeks
skeletal muscle tissue lipid intermediates (e.g., ceramide, diacylglycerol, acylcarnitine concentrations)
Time frame: 3 weeks
Adipose tissue inflammation measures (e.g., interleukin (IL)-6, and -8, adiponectin, TNF-alpha, nuclear factor-kappa b, gene and protein expression)
Time frame: 3 weeks
Skeletal muscle inflammation measures (e.g., IL-6,8, TNF-alpha, nuclear factor-kappa b gene and protein expression)
Time frame: 3 weeks
Adipose tissue arteriole function (vasodilation measurement)
Time frame: 3 weeks
Changes in skeletal muscle insulin signaling pathway
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2024.
- Individual participant dataSharing planned: No. Subject to VA regulation.
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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.
Peter D Reaven, MD principal investigator
Carl T. Hayden Medical Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liraglutide and Sugar Pill in people with Insulin Resistance, run by Phoenix VA Health Care System 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 4 inclusion and 16 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 22 Jul 2024. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Whole Body Insulin Sensitivity (insulin suppression test) (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jul 2024.