Exenatide (Byetta ®) Regulation of Intestinal and Hepatic Lipoprotein Particle Production in Humans
Tracking Information | |||||
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First Received Date ICMJE | November 12, 2009 | ||||
Last Updated Date | June 21, 2012 | ||||
Start Date ICMJE | January 2010 | ||||
Primary Completion Date | September 2011 (final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
The objective is to examine the change in apoB48 production rate after one subcutaneous injection of exenatide, under conditions of a pancreatic clamp and a steady state fed state. [ Time Frame: over 10 hours ] [ Designated as safety issue: No ] | ||||
Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | Complete list of historical versions of study NCT01056549 on ClinicalTrials.gov Archive Site | ||||
Current Secondary Outcome Measures ICMJE |
The secondary objective is to examine the change in apoB100 production rate in the same conditions, and the secondary measure is the difference between exenatide and placebo in the mean production of TRL-apoB100 [ Time Frame: over 10 hours ] [ Designated as safety issue: No ] | ||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Outcome Measures ICMJE | |||||
Original Other Outcome Measures ICMJE | |||||
Descriptive Information | |||||
Brief Title ICMJE | Exenatide (Byetta ®) Regulation of Intestinal and Hepatic Lipoprotein Particle Production in Humans | ||||
Official Title ICMJE | Exenatide (Byetta ®) Regulation of Intestinal and Hepatic Lipoprotein Particle Production in Humans. | ||||
Brief Summary | Exenatide acutely inhibits intestinal lipoprotein particle production. We are unable to speculate whether exenatide affects hepatic lipoprotein production in humans since there is currently no evidence from animal models or in vitro studies that have demonstrated an effect |
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Detailed Description | Subjects will receive an infusion of stable isotope enriched acetate, leucine and a bolus of glycerol in order to measure the rates of fatty acid synthesis, apolipoprotein and triglyceride turnover respectively. This in vivo stable isotope enrichment methodology has been widely established and used by investigators around the world for more than 30 years to examine the metabolism of various metabolites in humans. Following an overnight fast, at approximately 9am on day 1 of the study the subject will be admitted to hospital and will have a 30ml fasting blood sample drawn for analysis of plasma glucose, total plasma cholesterol, LDL-cholesterol, HDL cholesterol, triglycerides (TG), free fatty acids (FFA), insulin, GLP-1, growth hormone, glucagon, stable isotope enrichment and a more detailed analysis of triglyceride rich lipoprotein (TRL) composition (lipid and apolipoprotein content). A radio-opaque polyvinyl feeding tube (Entriflex NG Tube 55'' [140cm] 10fr Item # 8884721055, Kendall Products, Tyco Healthcare, Toronto, ON) will be inserted through the nose into the stomach, with enough length provided for migration of the tip into the duodenum. The subject will be administered 10 mg metoclopramide orally to facilitate transport of the tip of the tube into the duodenum. The subject will be allowed to eat regular meals during the day but will fast overnight after 7pm and will remain fasting for the duration of the study. Water ad lib will be allowed. At approximately 3pm on day 1 an abdominal X-Ray will confirm the position of the tube in the duodenum. At 4pm 2 iv's will be inserted into a superficial vein in each forearm, one for infusion and one for sampling. An infusion of 1-13C acetate (15 gm in a bag of ½ N saline at 32ml/hr) will begin after the iv's have been inserted and will be infused for the remainder of the study, which is 27 hours. Starting at 4am a synthetic triglyceride emulsion, Intralipid (20% solution, Baxter Canada) , will be infused through the feeding tube into the duodenum at a rate of 40 ml/hr for the duration of the experiment (ie until 7pm that evening). This will provide a steady state fed state for the subsequent assessment of lipoprotein turnover kinetics. The subjects will receive, in random order, either exenatide 10 mg or equivalent volume of saline subcutaneously at 7am on day 2 of the hospitalization (i.e. at -2hr) during the first of the two studies. The pancreatic clamp will begin at 7am (-2hr), immediately following administration of either exenatide or saline and continue throughout the subsequent 12 hours (until 7pm). . During the pancreatic clamp the subjects will receive an iv infusion of glucagon (0.65ng/kg/min), growth hormone (Humatrope, 3.0 ng/kg/min), somatostatin (sandostatin, 25 µg/hr) and insulin (Novolin R, 0.05 mU/kg/min). At 9 am (we will refer to this time point as 0hr of the lipoprotein turnover study), the lipoprotein turnover study will begin. An iv bolus of deuterated-glycerol (d5-glycerol, 75 mmol/kg) will be administered, followed by a primed-constant infusion of deuterated leucine; d3-leucine, (10 mmol/kg bolus followed by 10 mmol/kg/hr for 10 hours). Blood samples will be collected prior to and at regular time intervals for 10 hours after the iv bolus of d3-glycerol and start of the constant infusion of d3-leucine (for assessment of lipoprotein kinetics). Blood samples will be collected prior to (30ml at -2hr, 10ml at -1hr and 30ml at 0hr) and 5min and 15min (10ml each) and then 30ml each at 30min, 1hr, 2hr, 3hr, 4hr, 5hr, 6hr (only 10ml),7hr, 8hr, 9hr and 10hr after administration of d5-glycerol and start of d3-leucine infusion. |
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Study Type ICMJE | Interventional | ||||
Study Phase | |||||
Study Design ICMJE | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Single Blind (Subject) Primary Purpose: Basic Science |
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Condition ICMJE | Hyperlipidemia | ||||
Intervention ICMJE | Drug: exenatide
In each study, the subjects will receive s.c. injection of either exenatide or matched placebo, in the Metabolic Testing Center and 2 hours prior to the start of the lipoprotein turnover study. Subjects will be blinded with regard to the treatments.
Other Name: Byetta |
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Study Arm (s) | Experimental: exenatide subcutaneous injection
Study A: lipoprotein turnover following subcutaneous exenatide administration, under conditions of pancreatic clamp. Study B: lipoprotein turnover study following subcutaneous placebo administration, under conditions of pancreatic clamp.
Intervention: Drug: exenatide |
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Publications * | Xiao C, Bandsma RH, Dash S, Szeto L, Lewis GF. Exenatide, a glucagon-like peptide-1 receptor agonist, acutely inhibits intestinal lipoprotein production in healthy humans. Arterioscler Thromb Vasc Biol. 2012 Jun;32(6):1513-9. Epub 2012 Apr 5. | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Enrollment ICMJE | 15 | ||||
Completion Date | September 2011 | ||||
Primary Completion Date | September 2011 (final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||
Ages | 18 Years to 60 Years | ||||
Accepts Healthy Volunteers | Yes | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Location Countries ICMJE | Canada | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT01056549 | ||||
Other Study ID Numbers ICMJE | REB 09-0428-B | ||||
Has Data Monitoring Committee | No | ||||
Responsible Party | Gary Lewis, University Health Network, Toronto | ||||
Study Sponsor ICMJE | University Health Network, Toronto | ||||
Collaborators ICMJE | Eli Lilly and Company | ||||
Investigators ICMJE |
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Information Provided By | University Health Network, Toronto | ||||
Verification Date | June 2012 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |