Exenatide (Byetta ®) Regulation of Intestinal and Hepatic Lipoprotein Particle Production in Humans

NCT01056549 | Completed

• 1 other identifier: REB 09-0428-B
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Conditions

Hyperlipidemia

Keywords

Intestinal lipoprotein; Apo B48 and apoB100; Pancreatic clamp; GLP-1 agonist

Outcome Measures

Primary Outcomes (1)

• 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.

  over 10 hours

Secondary Outcomes (1)

• 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

  over 10 hours

Study Arms (1)

exenatide subcutaneous injection

EXPERIMENTAL

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.

Drug: exenatide

Interventions

exenatide DRUG

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.

Also known as: Byetta

exenatide subcutaneous injection

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women, aged 18 to 60 years
• Body mass index 20 kg/m2 to 25 kg/m2
• Hemoglobin above 130g/L.
• Normal glucose tolerance in response to a 75g, 2-hr OGTT

You may not qualify if:

• Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.
• Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr \> 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP \> 100 or systolic \> 180) or proliferative retinopathy
• History of diabetes or OGTT indicative of diabetes or impaired glucose tolerance.
• Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.
• Any laboratory values: AST \> 2x ULN; ALT \> 2x ULN TSH \> 6 mU/l
• Current addiction to alcohol or substances of abuse as determined by the investigator.
• Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
• Taking any prescription or non-prescription medications at the time of the study
• Having donated blood three months prior to and three months post study procedures
• A pregnancy test will be performed 1 to 3 days prior to each study in all female subjects. Those who test positive for pregnancy will be excluded.
• No clinical evidence of neoplasms which have been known to overexpress GLP-1 receptors i.e. pheochromocytomas, brain tumors and embryonic tumors.
• Hypersensitivity to egg-, soya-,or peanut protein or previous allergy to intralipid
• Those with known sensitivity to metoclopramide

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (1)

• 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. doi: 10.1161/ATVBAHA.112.246207. Epub 2012 Apr 5.

  PMID: 22492091 DERIVED

MeSH Terms

Conditions

Hyperlipidemias

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• gary F Lewis, MD, FRCPC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Medicine and Physiology

Study Record Dates

• First Submitted: November 12, 2009
• First Posted: January 26, 2010
• Study Start: January 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: June 22, 2012

Record last verified: 2012-06

Locations

CA (1)