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Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers (APELINS-2)

Primary Purpose

Diabetes

Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
apelin
placebo
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetes focused on measuring Type 2 diabetic volunteers

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Clinical diagnosis of type2 diabetes
  • Body Mass Index between 27 and 33 kg / cm ²
  • HbA1c < 8.5%
  • Non-pathological Electrocardiogram
  • Heart rate between 50 and 80 beats per minute at rest.
  • Complete Blood Count (CBC) with no significant anomaly in terms of the investigator..
  • Serum electrolytes without clinically significant abnormalities in terms of the investigator.
  • Liver function tests without clinically significant abnormalities in terms of the investigator
  • Renal function tests without clinically significant abnormalities in terms of the investigator
  • Good peripheral vein (forearm and back of the hand).
  • Agreement to participate in the establishment of a serum bank.
  • Ability to sign informed consent.
  • Affiliation to a social security scheme

Exclusion Criteria:

  • Secondary prevention of cardio-vascular disease
  • Insulin therapy or Glucagon Like Peptid 1 (GLP-1) analogs therapy in the 6 months before inclusion.
  • Risk factor, treatment or electrocardiogram as recommended by International Conference on Harmonization (ICH) E14 "Clinical Evaluation of QT / QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs"
  • Repeated a QTc interval> 450 ms measurement
  • Risk factor for torsade de pointes: myocardial infarction, hypokalemia, family history of long QT syndrome
  • Personal history of cancer.
  • Positive HIV serology.
  • Hepatitis B serology positive.
  • Positive hepatitis C serology.
  • Cognitive impairment or mental illness (at the discretion of the investigator).
  • Chronic excessive alcohol consumption (consumption > 30g/day or 210g/week).
  • Person under judicial protection, guardianship.
  • Subject with a resting systolic blood pressure greater than 140 mm Hg and diastolic blood pressure greater than 90 mmHg
  • Smoking more than 10 cigaret per day and can not be interrupted for 24 hours.

Sites / Locations

  • University Hospitals of Toulouse (Rangueil)

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Apelin then Placebo

Placebo then Apelin

Arm Description

First clamp during which an apelin infusion will be administered followed by a wash-out period and then, a second clamp in which a placebo infusion will be administered

First clamp during which a placebo infusion will be administered followed by a wash-out period and then, a second clamp in which an apelin infusion will be administered

Outcomes

Primary Outcome Measures

Delta between Glucose Infusion Rate
Difference between glucose infusion rate measured during investigational product infusion (mean of values measured at 210, 215, 220, 225, 230, 235 and 240 minutes) and basal glucose infusion rate (mean of values measured at 90, 95, 100, 105, 110, 115 and 120 minutes).

Secondary Outcome Measures

Measure of M-value (a glucose physiological parameter)
Difference between value of product time (mean of values measured at 210, 215, 220, 225, 230, 235 and 240 minutes) and value of basal (mean of values measured at 90, 95, 100, 105, 110, 115 and 120 minutes).
systolic blood pressure and diastolic blood pressure
heart rate
Measure of QTc interval with electrocardiogram examination
Clinic sign of apelin intolerance
Dosage of plasma proteins
A kinetic is realized with samples at 0, 15, 30, 45, 60, 75, 90, 100, 110, 120, 135, 150, 165, 180, 195, 200, 220, 230 and 240 minutes
Clinic sign of apelin allergy
Modification in physiological parameters
Clinic sign of apelin toxicity
Modification in physiological parameters

Full Information

First Posted
March 18, 2016
Last Updated
August 21, 2017
Sponsor
University Hospital, Toulouse
Collaborators
Société Francophone du Diabète
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1. Study Identification

Unique Protocol Identification Number
NCT02724566
Brief Title
Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers
Acronym
APELINS-2
Official Title
Influence of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
May 2016 (Actual)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
April 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
Collaborators
Société Francophone du Diabète

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Preclinical studies have demonstrated in mouse models that (PYR1)-apelin-13 exerts a glucose-regulating action in vivo. The (PYR1)-apelin-13 effect on insulin sensitivity in healthy overweighed volunteers has been previously assessed in a phase I clinical trial (APELINS study; NCT02033473). The APELINS-2 clinical trial aims to expand the initial proof of concept to the population targeted by future innovative insulin-sensitizing therapies: patients living with type 2 diabetes.
Detailed Description
Insulin sensitivity is measured using the hyperinsulinemic euglycemic glucose clamp method. The hypothesis of the investigators is that a continuous (pyr1)-apelin-13 infusion improves insulin sensitivity of type 2 diabetic patients compared to placebo infusion. This study could bring new elements for understanding the pathophysiology of insulin resistance and type 2 diabetes mellitus in humans and could lead to the development of innovative therapies in type 2 diabetes mellitus.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes
Keywords
Type 2 diabetic volunteers

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Apelin then Placebo
Arm Type
Other
Arm Description
First clamp during which an apelin infusion will be administered followed by a wash-out period and then, a second clamp in which a placebo infusion will be administered
Arm Title
Placebo then Apelin
Arm Type
Other
Arm Description
First clamp during which a placebo infusion will be administered followed by a wash-out period and then, a second clamp in which an apelin infusion will be administered
Intervention Type
Drug
Intervention Name(s)
apelin
Other Intervention Name(s)
[pyr1]-apelin-13 infusion
Intervention Description
Assessing the difference between the insulin sensitivity measured during hyperinsulinemic euglycemic clamps in the presence of a 2 hours continuous infusion of (PYR1)-apelin-13 (30nmol/kg) versus a 2 hours continuous infusion of placebo (vehicle alone).
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
2 hours continuous infusion of placebo (vehicle alone) to compare with 2 hours infusion of apelin
Primary Outcome Measure Information:
Title
Delta between Glucose Infusion Rate
Description
Difference between glucose infusion rate measured during investigational product infusion (mean of values measured at 210, 215, 220, 225, 230, 235 and 240 minutes) and basal glucose infusion rate (mean of values measured at 90, 95, 100, 105, 110, 115 and 120 minutes).
Time Frame
240 minutes
Secondary Outcome Measure Information:
Title
Measure of M-value (a glucose physiological parameter)
Description
Difference between value of product time (mean of values measured at 210, 215, 220, 225, 230, 235 and 240 minutes) and value of basal (mean of values measured at 90, 95, 100, 105, 110, 115 and 120 minutes).
Time Frame
240 minutes
Title
systolic blood pressure and diastolic blood pressure
Time Frame
240 minutes
Title
heart rate
Time Frame
240 minutes
Title
Measure of QTc interval with electrocardiogram examination
Time Frame
240 minutes
Title
Clinic sign of apelin intolerance
Time Frame
240 minutes
Title
Dosage of plasma proteins
Description
A kinetic is realized with samples at 0, 15, 30, 45, 60, 75, 90, 100, 110, 120, 135, 150, 165, 180, 195, 200, 220, 230 and 240 minutes
Time Frame
240 minutes
Title
Clinic sign of apelin allergy
Description
Modification in physiological parameters
Time Frame
240 minutes
Title
Clinic sign of apelin toxicity
Description
Modification in physiological parameters
Time Frame
240 minutes

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinical diagnosis of type2 diabetes Body Mass Index between 27 and 33 kg / cm ² HbA1c < 8.5% Non-pathological Electrocardiogram Heart rate between 50 and 80 beats per minute at rest. Complete Blood Count (CBC) with no significant anomaly in terms of the investigator.. Serum electrolytes without clinically significant abnormalities in terms of the investigator. Liver function tests without clinically significant abnormalities in terms of the investigator Renal function tests without clinically significant abnormalities in terms of the investigator Good peripheral vein (forearm and back of the hand). Agreement to participate in the establishment of a serum bank. Ability to sign informed consent. Affiliation to a social security scheme Exclusion Criteria: Secondary prevention of cardio-vascular disease Insulin therapy or Glucagon Like Peptid 1 (GLP-1) analogs therapy in the 6 months before inclusion. Risk factor, treatment or electrocardiogram as recommended by International Conference on Harmonization (ICH) E14 "Clinical Evaluation of QT / QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs" Repeated a QTc interval> 450 ms measurement Risk factor for torsade de pointes: myocardial infarction, hypokalemia, family history of long QT syndrome Personal history of cancer. Positive HIV serology. Hepatitis B serology positive. Positive hepatitis C serology. Cognitive impairment or mental illness (at the discretion of the investigator). Chronic excessive alcohol consumption (consumption > 30g/day or 210g/week). Person under judicial protection, guardianship. Subject with a resting systolic blood pressure greater than 140 mm Hg and diastolic blood pressure greater than 90 mmHg Smoking more than 10 cigaret per day and can not be interrupted for 24 hours.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre Gourdy, PhD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals of Toulouse (Rangueil)
City
Toulouse
State/Province
Midi-Pyrénées
ZIP/Postal Code
31059
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

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