- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03818178
Intramyocellular Fatty Acid Trafficking in Insulin Resistance States - Effects of Intestinal Delivery of Lipids
Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking is responsible for muscle insulin resistance, although it has been shown that raising FFA with Intralipid can cause muscle insulin resistance within 4 hours. The investigators do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. The investigators propose to alter the profile and concentrations of FFA of healthy, non-obese adults using an overnight, intra-duodenal palm oil infusion vs. an overnight intra-duodenal Intralipid infusion (both compared to saline control). The investigators will compare the muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates, providing the first measure of how different FFA profiles alter muscle FFA trafficking and insulin action at the whole body and cellular/molecular levels. By identifying which steps in the insulin signaling pathway are most affected, the investigators will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance.
Hypothesis 1: Palm oil infusion will result in abnormal FFA trafficking into intra-myocellular ceramides and abnormal insulin signaling.
Hypothesis 2: Intralipid infusion will result in abnormal FFA trafficking into intra-myocellular saturated DG and abnormal insulin signaling.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Pamela Reich
- Phone Number: 507-255-6062
- Email: reich.pamela@mayo.edu
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Recruiting
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Women and Men (Women premenopausal)
- BMI 18-27
- Weight stable
- Not pregnant/nursing
Exclusion Criteria:
- Ischemic heart disease
- Atherosclerotic valvular disease
- Smokers (> 20 cigarettes per week)
- Bilateral oophorectomy
- Concomitant use of medications that can alter serum lipid profile (high dose fish oil, statins, niacin, fibrates, thiazolinediones, beta-blockers, atypical antipsychotics)
- Lidocaine allergy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Saline
|
All participants will serve as their own controls with a saline infusion study day.
|
Experimental: Intralipid
|
Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.
|
Experimental: Palm Oil
|
Half of the participants will receive either naso-duodenal infusion of intralipid or palm oil each participant will serve as their own saline control on the second study day.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in fatty acid enrichment of intramyocellular signaling molecules before and after a euglycemic, hyperinsulinemic clamp
Time Frame: 18 hours
|
The study involves the use of a hyperinsulinemic, euglycemic clamp to compare fatty acid enrichments in intramyocellular signaling molecules.
The first half of the study will be the "pre-clamp" stage.
During this stage, volunteers will receive an intravenous infusion of C13-labelled palmitate as a tracer in order for enrichment calculations to be performed pre-clamp.
One muscle biopsy will be obtained to measure fatty acid enrichment within intramyocellular ceramides, diacylglycerols, long-chain acylcarnitines, and intramyocellular triglycerides.
The insulin clamp will then commence, and volunteers will simultaneously receive an intravenous infusion of a second tracer, D-9 palmitate.
This tracer will allow us to calculate enrichments during the insulin clamp stage of the study.
A second muscle biopsy will be performed at the end of the insulin clamp, and similar enrichment calculations will be performed.
|
18 hours
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18-002520
- 5R01DK045343-27 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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