Drug Trial of Lixisenatide on Gastric Emptying and Blood Pressure Drops in Type 2 Diabetics and Healthy People (Lixi)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Effects of Lixisenatide on Gastric Emptying, Glycaemia and 'Postprandial' Blood Pressure in Type 2 Diabetes and Healthy Subjects.|
- Blood Pressure [ Time Frame: 4.5 hours per study ] [ Designated as safety issue: No ]Systolic and diastolic blood pressure (mmHg)
- Heart rate [ Time Frame: 4.5 hours per study ] [ Designated as safety issue: No ]Heart rate (beats per minute)
- Gastric emptying rate [ Time Frame: 3 hours per study ] [ Designated as safety issue: No ]Gastric retention (percent in the total stomach)
- Blood glucose concentration [ Time Frame: 3 hours per study ] [ Designated as safety issue: No ]Blood glucose (mmol/L)
- Intragastric distribution [ Time Frame: 3 hours per study ] [ Designated as safety issue: No ]percent retention in the proximal and distal stomach
- Gastrointestinal hormone release (concentrations of GLP-1, GIP, C-peptide and 3-OMG) [ Time Frame: 4.5 hours per study ] [ Designated as safety issue: No ]concentrations of GLP-1, GIP, C-peptide and 3-OMG
- Superior mesenteric artery blood flow [ Time Frame: 3.5 hours per study ] [ Designated as safety issue: No ]Doppler ultrasound (ml/min)
- Appetite (visual analogue questionnaire) [ Time Frame: 4.5 hours per study ] [ Designated as safety issue: No ]sensations of hunger, fullness, desire to eat (mm)
- Cardiac output [ Time Frame: 3.5 hours per study ] [ Designated as safety issue: No ]Finapres (L)
- Stroke volume [ Time Frame: 3.5 hours per study ] [ Designated as safety issue: No ]Finapres (L)
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||April 2016|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Lixisenatide
Lixisenatide: 10 mcg, one subcutaneous injection dose
Other Name: Lyxumia
Placebo Comparator: Placebo
Matching placebo: one subcutaneous injection dose
Other Name: Dummy
Lixisenatide is a drug that has been shown to reduce postprandial glycaemia in people with type 2 diabetes and is now approved for use in Australia. Although slowing of gastric emptying is likely to be the dominant mechanism by which lixisenatide reduces postprandial glycaemia after a meal, the effects of lixisenatide on gastric emptying have hitherto not been quantified by the 'gold standard' technique of scintigraphy. The study would determine and evaluate for the first time the magnitude of, and the relationship between lixisenatide on glycaemia with those on gastric emptying with scintigraphy. This information will be of fundamental significance to the effective use of lixisenatide in the management of people with type 2 diabetes that suffer from postprandial hypotension.
Postprandial hypotension represents an important clinical disorder that occurs frequently in the elderly and people with type 2 diabetes and for which current management is suboptimal. While the mechanisms mediating postprandial hypotension are poorly understood, impaired regulation of splanchnic blood flow, gastric distension, the rate of small intestinal delivery and neural and hormonal mechanisms have been identified as possible pathophysiological mechanisms. Meal ingestion is associated with splanchnic blood pooling and a consequent reduction in venous return of blood to the heart. In healthy young and older individuals, with intact baroreflex mechanisms, these changes induce a rise in heart rate, stoke volume and cardiac output leading to a compensatory rise in blood pressure. However, patients with postprandial hypotension, these responses are inadequate to maintain blood pressure. The magnitude of the fall in blood pressure is greater when gastric emptying is more rapid and that slowing gastric emptying can markedly attenuate the postprandial fall in blood pressure in both healthy older subjects and type 2 patients.
There is currently no information about the effect of lixisenatide on postprandial blood pressure and splanchnic blood flow in patients with type 2 diabetes.
The purpose of this study would determine whether lixisenatide reduces the postprandial fall in blood pressure and related effects of gastric emptying to those on blood pressure, heart rate and splanchnic blood flow.
The use of lixisenatide on appetite and energy intake and how these relate to effects of gastric emptying is lacking.
It is hypothesized that lixisenatide will slow gastric emptying of oral glucose; attenuate both fasting and the postprandial rise in blood glucose; attenuate the magnitude of the fall in blood pressure, rise in heart rate and increase in SMA flow and reduce hunger, increase fullness and decrease energy intake at a buffet meal with greater effects in patients with type 2 diabetes that healthy subjects.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02308254
|Contact: Rachael S Tippett, BSc Honours||8222 2915 ext firstname.lastname@example.org|
|Contact: Laurence G Trahair, BHlthSci Hon||8222 2915 ext email@example.com|
|Australia, South Australia|
|Discipline of Medicine, Royal Adelaide Hospital||Recruiting|
|Adelaide, South Australia, Australia, 5000|
|Contact: Karen L Jones, PhD +61 8 8222 5394 ext 25394 firstname.lastname@example.org|
|Contact: Michael Horowitz, PhD, FRACP +61 8 8222 4327 ext 24327 email@example.com|
|Principal Investigator: Karen L Jones, PhD|
|Sub-Investigator: Laurence G Trahair, BHlthSci Hon|
|Sub-Investigator: Rachael S Tippett, BSc Honours|
|Sub-Investigator: Chris Rayner, PhD, FRACP|
|Sub-Investigator: Michael Horowitz, PhD, FRACP|
|Principal Investigator:||Karen L Jones, PhD||University of Adelaide, Royal Adelaide Hospital|