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Drug Trial of Lixisenatide on Gastric Emptying and Blood Pressure Drops in Type 2 Diabetics and Healthy People (Lixi)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Royal Adelaide Hospital
Sponsor:
Collaborators:
Sanofi
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Karen Jones, Royal Adelaide Hospital
ClinicalTrials.gov Identifier:
NCT02308254
First received: November 3, 2014
Last updated: October 27, 2015
Last verified: October 2015
  Purpose
The purpose of this study is to determine the effects of the drug lixisenatide on blood sugar levels, stomach emptying, blood pressure and heart rate, release of gut hormones and blood flow in the gut after a glucose drink in both healthy subjects and people with type 2 diabetes. If lixisenatide is shown to be effective, it would encourage ongoing evaluation of its potential use in the management of the falls in blood pressure following a meal in diabetic patients.

Condition Intervention Phase
Diabetes Mellitus
Gastroparesis
Drug: Lixisenatide
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Royal Adelaide Hospital:

Primary Outcome Measures:
  • Blood Pressure [ Time Frame: 4.5 hours per study ] [ Designated as safety issue: No ]
    Systolic and diastolic blood pressure (mmHg)


Secondary Outcome Measures:
  • 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)


Other Outcome Measures:
  • 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)


Estimated Enrollment: 30
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)
Arms Assigned Interventions
Active Comparator: Lixisenatide
Lixisenatide: 10 mcg, one subcutaneous injection dose
Drug: Lixisenatide
Abdominal administration
Other Name: Lyxumia
Placebo Comparator: Placebo
Matching placebo: one subcutaneous injection dose
Drug: Placebo
Abdominal administration
Other Name: Dummy

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy subjects:

    • Male or female (females using appropriate contraceptive method or willing to undergo pregnancy test)
    • Body Mass Index (BMI) 19 - 30 kg/m2
  • Type 2 Diabetic Patients:

    • As per "healthy subjects"
    • Type 2 diabetes (World Health Organisation (WHO) criteria) managed by diet alone or on metformin
    • Glycated haemoglobin >6.0% and <8.5%

Exclusion Criteria:

  • Subjects with a history of severe respiratory, cardiovascular, hepatic and/or renal disease (severe in that the social or physical manifestations of the disease, or living with the condition, impact negatively and significantly on the individuals' ability to lead a normal day to day life), chronic alcohol abuse or epilepsy (excluded by history) or if iron status, or liver function tests are outside the following ranges:

    1. Alanine aminotransferase (ALT) 0 - 55 U/L
    2. Alkaline phosphatase 30 - 110 U/L
    3. Aspartate transaminase 0 - 45 U/L
    4. Amylase and/or lipase >3 x ULN
    5. Bilirubin 6 - 24 mmol/L
    6. Ferritin 15 - 200 ng/mL (females); 30 - 300 ng/mL (males)
    7. Haemoglobin 115 - 155 g/L (females); 135 - 172 g/L (males)
  • Subjects with a creatinine clearance cut-off of <50 ml/min
  • Subjects requiring medication likely to influence blood pressure or gastrointestinal function
  • Subjects with a past history of gastrointestinal disease, including known gastroparesis, significant upper gastrointestinal symptoms and previous gastric surgery
  • Subjects with a past history of unexplained pancreatitis, chronic pancreatitis, pancreatectomy
  • Subjects with a current or prior history of c-cell carcinoma
  • Smoking > 10 cigarettes/day
  • Alchohol consumption > 20 g/day
  • Subjects who have donated blood in the previous 12 weeks
  • Women of childbearing potential with no effective contraceptive method (defined as premenopausal, not surgically sterile women for at least 3 months prior to the time of screening) must have a confirmed negative urine B-hCG pregnancy test at screening visit. They must also use an effective contraceptive method throughout the study, and agree to repeat urine pregnancy test at designated visits.
  • Lactation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02308254

Contacts
Contact: Rachael S Tippett, BSc Honours 8222 2915 ext 2915 rachael.tippett@adelaide.edu.au
Contact: Laurence G Trahair, BHlthSci Hon 8222 2915 ext 2915 laurence.trahair@adelaide.edu.au

Locations
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    karen.jones@adelaide.edu.au   
Contact: Michael Horowitz, PhD, FRACP    +61 8 8222 4327 ext 24327    michael.horowitz@adelaide.edu.au   
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         
Sponsors and Collaborators
Royal Adelaide Hospital
Sanofi
National Health and Medical Research Council, Australia
Investigators
Principal Investigator: Karen L Jones, PhD University of Adelaide, Royal Adelaide Hospital
  More Information

Publications:
Riddle M, Home P, Marre M, Niemoeller E, Ping L, Rosenstock J. Efficacy and safety of once-daily lixisenatide in type 2 diabetes insufficiently controlled with basal insulin ± metformin: GetGoal-L Study. Diabetes 2012;61(Suppl 1):A212-A344 (Abstract 983-P).
Rosenstock J, Forst T, Aronson R, et al. Efficacy and safety of once-daily lixisenatide added on to titrated glargine plus oral agents in type 2 diabetes: GetGoal-Duo 1 Study. Presented at the 72nd Scientific Sessions of the American Diabetes Association, Philadelphia PA, 8-12 June 2012 (Abstract 62-OR).
Ahrén B, Dimas L, Miossec P, Saubado S, Aronson R. Efficacy and safety of lixisenatide QD morning and evening injections vs placebo in T2DM inadequately controlled on metformin (GetGoal-M). Oral presentation at the 21st World Diabetes Congress, Dubai, UAE, 8 December 2011 (Abstract 0-0591).
Ratner R, Hanefield M, Shamanna P, et al. Efficacy and safety of lixisenatide once daily versus placebo in patients with T2DM insufficiently controlled on sulfonylurea + metformin (GetGoal-S). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1):1-542 (Abstract 785).
Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Aronson R. Efficacy and safety of lixisenatide once daily versus placebo in patients with type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes 2012;61(Suppl 1):A212-A344 (Abstract 1010-P).
Rosenstock J, Raccah D, Koranyi L, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in patients with T2DM insufficiently controlled on metformin (GetGoal-X). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1):1-542 (Abstract 786).
Bolli G, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Hanefield M. Efficacy and safety of lixisenatide once-daily versus placebo in patients with T2DM insufficiently controlled on metformin (GetGoal-F1). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1): 1-542 (Abstract 784).

Responsible Party: Karen Jones, Professor, Royal Adelaide Hospital
ClinicalTrials.gov Identifier: NCT02308254     History of Changes
Other Study ID Numbers: 130419 
Study First Received: November 3, 2014
Last Updated: October 27, 2015
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Royal Adelaide Hospital:
Blood pressure
Gastric emptying
Glycemia
Appetite
Incretin Hormones
Superior mesenteric artery blood low

Additional relevant MeSH terms:
Diabetes Mellitus
Gastroparesis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on December 02, 2016