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

October 27, 2015 updated by: Karen Jones, Royal Adelaide Hospital

Effects of Lixisenatide on Gastric Emptying, Glycaemia and 'Postprandial' Blood Pressure in Type 2 Diabetes and Healthy Subjects.

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.

Study Overview

Status

Unknown

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Discipline of Medicine, Royal Adelaide Hospital
        • Contact:
        • Contact:
        • 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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Lixisenatide
Lixisenatide: 10 mcg, one subcutaneous injection dose
Abdominal administration
Other Names:
  • Lyxumia
PLACEBO_COMPARATOR: Placebo
Matching placebo: one subcutaneous injection dose
Abdominal administration
Other Names:
  • Dummy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Pressure
Time Frame: 4.5 hours per study
Systolic and diastolic blood pressure (mmHg)
4.5 hours per study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heart rate
Time Frame: 4.5 hours per study
Heart rate (beats per minute)
4.5 hours per study
Gastric emptying rate
Time Frame: 3 hours per study
Gastric retention (percent in the total stomach)
3 hours per study
Blood glucose concentration
Time Frame: 3 hours per study
Blood glucose (mmol/L)
3 hours per study

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intragastric distribution
Time Frame: 3 hours per study
percent retention in the proximal and distal stomach
3 hours per study
Gastrointestinal hormone release (concentrations of GLP-1, GIP, C-peptide and 3-OMG)
Time Frame: 4.5 hours per study
concentrations of GLP-1, GIP, C-peptide and 3-OMG
4.5 hours per study
Superior mesenteric artery blood flow
Time Frame: 3.5 hours per study
Doppler ultrasound (ml/min)
3.5 hours per study
Appetite (visual analogue questionnaire)
Time Frame: 4.5 hours per study
sensations of hunger, fullness, desire to eat (mm)
4.5 hours per study
Cardiac output
Time Frame: 3.5 hours per study
Finapres (L)
3.5 hours per study
Stroke volume
Time Frame: 3.5 hours per study
Finapres (L)
3.5 hours per study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Karen L Jones, PhD, University of Adelaide, Royal Adelaide Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (ANTICIPATED)

April 1, 2016

Study Completion (ANTICIPATED)

April 1, 2016

Study Registration Dates

First Submitted

November 3, 2014

First Submitted That Met QC Criteria

December 2, 2014

First Posted (ESTIMATE)

December 4, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

October 29, 2015

Last Update Submitted That Met QC Criteria

October 27, 2015

Last Verified

October 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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