Tissue Lipids and Insulin Resistance
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|ClinicalTrials.gov Identifier: NCT00483210|
Recruitment Status : Withdrawn (The study goals were accomplished by a similar study at UAMS. (W.J. Evans))
First Posted : June 6, 2007
Last Update Posted : March 4, 2015
|First Submitted Date ICMJE||June 4, 2007|
|First Posted Date ICMJE||June 6, 2007|
|Last Update Posted Date||March 4, 2015|
|Study Start Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00483210 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Tissue Lipids and Insulin Resistance|
|Official Title ICMJE||Tissue Lipids and Insulin Resistance|
Resistance to the hypoglycemic action of insulin develops within 7 days of bedrest in young, healthy volunteers. We propose that the same event occurs in elderly individuals confined to bed, that alterations in lipid metabolism are, at least in part, responsible for the insulin resistance associated with bedrest, and that the accumulation of intracellular triglyceride (TG) in liver and muscle will play a role in impairing insulin action. Further, we propose that the PPARα (Peroxisome Proliferator-Activated Receptor Alpha) agonist fenofibrate will increase tissue fatty acid disposal by activating mitochondrial oxidative capacity, thereby improving insulin sensitivity.
We will investigate a series of specific hypotheses designed to examine the role of altered lipid metabolism in the development of insulin-resistance associated with bedrest. Further, since inactivity is likely a principal factor in the development of insulin resistance in the elderly, the response to the inactivity imposed by bedrest represents an acceleration of the normal development of insulin resistance in elderly individuals. Therefore, the results of this study will also be pertinent to the understanding of the mechanisms responsible for the natural development of insulin resistance in free-living elderly.
The accumulation of intracellular lipid reflects a dysregulation of tissue fatty acid metabolism involving abnormal relationships between tissue fatty acid uptake and oxidation. It has been postulated that such dysregulation of lipid metabolism causes insulin resistance as a direct consequence of the accumulated intracellular triglyceride (TG), or that the increased intracellular TG reflects an increase in active products of fatty acids, such as diacylglycerol, that inhibit the insulin signaling pathway. We recently found that both muscle and liver intracellular TG concentrations were elevated in more than one-half of otherwise healthy elderly individuals.
We hypothesize that an increase in tissue lipids in the elderly reflects altered tissue lipid metabolism that puts them at high risk for the development of insulin resistance with bedrest. Further, we propose that the PPARα (Peroxisome Proliferator-Activated Receptor Alpha) agonist fenofibrate will increase tissue fatty acid disposal by activating mitochondrial oxidative capacity, thereby improving insulin sensitivity.
We will examine the role of alterations in lipid metabolism in the development of insulin resistance that occurs with bedrest.
Methods: A total of 40 elderly subjects ranging in age from 60-85 will be studied. Subjects will be randomized to one of two groups: 1) 10 days of bedrest or 2) 10 days of bedrest plus fenofibrate. Each of the subjects will complete a 5- day diet stabilization period and have a metabolic infusion study on day 5, followed by 10 days of bedrest and a metabolic study on day 18. This will be followed by a 3 week rehabilitation program. Pre-test and post bedrest measurements include body composition by DEXA, intracellular TG measurements by MRS, strength testing.
The results will provide insight into the mechanisms responsible for the development of insulin resistance with inactivity and strategies for ameliorating this response.
|Study Type ICMJE||Interventional|
|Study Phase||Not Applicable|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Tissue Lipid Metabolism|
|Intervention ICMJE||Drug: Fenofibrate|
|Study Arms||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE||Not Provided|
|Study Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||60 Years to 85 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Not Provided|
|Removed Location Countries|
|NCT Number ICMJE||NCT00483210|
|Other Study ID Numbers ICMJE||72495|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Carole Hamon, University of Arkansas for Medical Sciences|
|Study Sponsor ICMJE||University of Arkansas|
|Collaborators ICMJE||National Institutes of Health (NIH)|
|PRS Account||University of Arkansas|
|Verification Date||March 2015|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP