APELINS: Effect of Apelin on Insulin Sensitivity: Proof of Concept in Healthy Volunteers
Study Details
Study Description
Brief Summary
The (PYR1)-apelin-13 is an endogenous peptide discovered relatively recently (1998). The apelin and its receptor, which is named apj, are expressed in many tissues including sensitive to the action of insulin, such as skeletal muscle, adipose tissue and heart tissue.
Recent work by the team of Prof. P.Valet (INSERM U1048, Toulouse) opened a new field of investigation, demonstrating for the first time in mouse models that apelin exerts a glucose-regulating in vivo action. The investigators propose a translational clinical research project whose goal is to provide the proof of concept of the favorable influence of apelin on insulin sensitivity in humans.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Apelin An apelin clamp in which an apelin infusion will be administered prior to reference clamp |
Drug: Apelin
An apelin clamp in which an apelin infusion will be administered
Drug: Placebo
A clamp reference during which a placebo solution (saline solution) will be administered
|
| Placebo Comparator: Placebo A clamp reference during which a placebo solution (saline solution) will be administered prior to apelin clamp |
Drug: Apelin
An apelin clamp in which an apelin infusion will be administered
Drug: Placebo
A clamp reference during which a placebo solution (saline solution) will be administered
|
Outcome Measures
Primary Outcome Measures
- Rate of glucose infusion [The last 30 minutes of a hyperinsulinemic euglycemic clamp]
Measuring the difference between the rate of glucose infusion measured in the last 30 minutes of a hyperinsulinemic euglycemic clamp in the presence of a continuous infusion (PYR1)-apelin-13 infusion rate of glucose measured in the same conditions in the presence of a continuous infusion of placebo.
Secondary Outcome Measures
- Calculation of the index of insulin sensitivity (Si) [During 240 minutes at visits 2 and 3]
- Changes in the measurement of systolic blood pressure during each clamp [During 240 minutes at visits 2 and 3]
- Changes in the measurement of diastolic blood pressure during each clamp [During 240 minutes at visits 2 and 3]
- Changes in heart rate measurement during each clamp [During 240 minutes at visits 2 and 3]
- Changes in ECG during each clamp [During 240 minutes at visits 2 and 3]
- Clinical signs of intolerance / allergy / toxicity at visit 2,3 and 4 [During 240 minutes at visits 2 and 3]
- Determination of plasma insulin at all sampling [During 240 minutes at visits 2 and 3]
- Determination of plasma glucagon at all sampling times [During 240 minutes at visits 2 and 3]
- Determination of plasma apelin at all sampling times [During 240 minutes at visits 2 and 3]
- Determination of plasma leptin at all sampling times [During 240 minutes at visits 2 and 3]
- Determination of plasma adiponectin at all sampling times [During 240 minutes at visits 2 and 3]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Men aged 18 to 40 years.
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BMI between 25 and 30 kg / cm ² (excluding terminals).
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Free of known chronic disease and any medication (any medication within 30 days prior to the inclusion visit).
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Non-pathological ECG.
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Heart rate between 50 and 80 beats per minute rest.
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Complete Blood Count (CBC) with no significant anomaly in terms of the investigator.
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Liver function tests without clinically significant abnormalities in terms of the investigator.
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Renal function tests without clinically significant abnormalities in terms of the investigator.
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Serum electrolytes without clinically significant abnormalities in terms of the investigator.
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Fasting plasma glucose less than 1.1 g / l.
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HbA1c within the normal range (4-6%).
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Good peripheral vein (forearm and back of the hand).
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Agreement to participate in the establishment of a serum bank.
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Sedentary or practicing occasional physical activity.
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Ability to sign informed consent.
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Affiliation to a social security scheme.
Exclusion Criteria:
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Risk factor, treatment or ECG as recommended by International Conference on Harmonization E14 (ICH E14) "Clinical Evaluation of QT / corrected QT interval (QTc Interval= Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs"
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Repeated a QTc interval> 450 ms measurement
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Risk factor: myocardial infarction, hypokalemia, family history of long QT syndrome
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Personal history of cancer.
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Positive HIV serology.
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Hepatitis B serology positive.
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Positive hepatitis C serology.
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Cognitive impairment or mental illness (at the discretion of the investigator).
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Chronic excessive alcohol consumption (consumption> 30g/jour or 210g/week).
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Person under judicial protection, guardianship.
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Subject with a resting systolic blood pressure greater than 140 mm Hg and diastolic blood pressure greater than 90 mmHg
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Smoking> 10 cig / day and can not be interrupted for 24 hours.
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Subject exclusion period of another protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital of Toulouse | Toulouse | France | 31059 |
Sponsors and Collaborators
- University Hospital, Toulouse
Investigators
- Principal Investigator: Pierre GOURDY, Md, PhD, University Hospital of Toulouse
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 13 182 03
- HAO 2013