The Effect of Liraglutide on Dietary Lipid Induced Insulin Resistance in Humans

July 18, 2024 updated by: Phoenix VA Health Care System
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
97

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

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

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85012
        • Carl T. Hayden VA Medical Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

36 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 40-75 years old
  2. Body mass index (BMI) from 22 to 35 kg/m2
  3. Normal glucose tolerance as determined by fasting blood glucose (< 100 mg/dl) and 75 gm glucose load (2 hr glucose <140 mg/dl)
  4. Fasting triglyceride levels ≥ 75 mg/dl and <500 mg/dl

Exclusion Criteria:

  1. Type 1 or 2 diabetes mellitus or a hemoglobin A1c value >6.5 mg/dl
  2. Any diabetes medications in the past month, thiazolidinedione medications in the prior 3 months or prior regular use of insulin
  3. Lactose intolerance or avoidance of dairy products
  4. 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)
  5. Known 'Nonalcoholic Fatty Liver Disease'
  6. Malabsorption of fat or other nutrients, severe lactose intolerance or other significant gastrointestinal or pancreatic problems (including history of acute or chronic pancreatitis).
  7. Recent history of nausea or vomiting
  8. Acute bacterial or viral illness or evidence of other active infection in the past 4 weeks
  9. Prior cardiovascular event, stable or unstable angina or other major illness in the past 6 months
  10. 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)
  11. Subjects receiving a lipid lowering medication must be on a stable dose for at least 6 weeks prior to participation.
  12. Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia 2
  13. Ethanol consumption more than 4 oz day
  14. Pregnancy, or lack of appropriate contraceptive use in premenopausal women (extremely rare in our older predominately male population)
  15. 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.
  16. BMI <22 and >35 kg/m2

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Liraglutide
Liraglutide titration up to 1.8 mg/d over approximately 3 weeks
Drug: Liraglutide
Subcutaneous injection by patient
Other Names:
  • Victoza
Placebo Comparator: Sugar pill
matching placebo and titration
Drug: Sugar Pill
Subcutaneous injection daily
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
3 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Postprandial lipid changes (area under the curve difference in triglyceride,total apolipoprotein B100, apolipoprotein B48, and apolipoprotein C3.
Time Frame: 3 weeks
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.
3 weeks
Postprandial changes in glucose metabolism (total and incremental area under the curve differences in glucose, insulin and glucagon)
Time Frame: 3 weeks
total and incremental area under the curve differences in glucose, insulin and glucagon between treatment arms
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
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.
3 weeks
subcutaneous adipose tissue lipid intermediates (e.g., ceramide, diacylglycerol, acylcarnitine concentrations)
Time Frame: 3 weeks
Adipose tissue biopsy samples will be used to compare lipid intermediates in placebo and liraglutide treatment phases.
3 weeks
skeletal muscle tissue lipid intermediates (e.g., ceramide, diacylglycerol, acylcarnitine concentrations)
Time Frame: 3 weeks
skeletal muscle tissue samples will be used to compare lipid intermediates in placebo and liraglutide treatment phases.
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
Adipose tissue biopsy samples will be used to compare inflammation measures in placebo and liraglutide treatment phases.
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
skeletal muscle tissue samples will be used to compare inflammation measures in placebo and liraglutide treatment phases
3 weeks
Adipose tissue arteriole function (vasodilation measurement)
Time Frame: 3 weeks
Adipose tissue biopsy samples will be used to isolate arterioles and measure ex vivo vascular function in placebo and liraglutide treatment phases.
3 weeks
Changes in skeletal muscle insulin signaling pathway
Time Frame: 3 weeks
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.
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Phoenix VA Health Care System

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novo Nordisk A/S

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Peter D Reaven, MD, Carl T. Hayden Medical Research Foundation

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 28, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 3, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 31, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 028
  • 1593855 (Other Identifier: Phoenix VA Health Care System IRBNet/VAIRRS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Subject to VA regulation.

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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