Overview

This trial is active, not recruiting.

Condition insulin resistance
Treatments liraglutide, sugar pill
Phase phase 4
Sponsor Phoenix VA Health Care System
Collaborator Novo Nordisk A/S
Start date March 2013
End date April 2016
Trial size 35 participants
Trial identifier NCT02403284, 028

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose basic science
Arm
(Experimental)
Liraglutide titration up to 1.8 mg/d over approximately 3 weeks
liraglutide Victoza
Subcutaneous injection by patient
(Placebo Comparator)
matching placebo and titration
sugar pill
Subcutaneous injection daily

Primary Outcomes

Measure
Whole Body Insulin Sensitivity (insulin suppression test)
time frame: 3 weeks

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants from 40 years up to 75 years old.

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

Additional Information

Official title The Effect of Liraglutide on Dietary Lipid Induced Insulin Resistance in Humans
Principal investigator Peter D Reaven, MD
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Phoenix VA Health Care System.