Effect of Apelin on Insulin Sensitivity: Proof of Concept in Healthy Volunteers

Healthy Clinical Trial

— APELINS  

Official title:

Effect of Apelin on Insulin Sensitivity: Proof of Concept in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02033473
• Other study ID #: 13 182 03
• Secondary ID: HAO 2013
• Status: Completed
• Phase: Phase 1
• Start date: January 2014
• Est. completion date: October 2014

Study information

• Verified date: July 2019
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Men aged 18 to 40 years.

• BMI between 25 and 30 kg / cm ² (excluding terminals).

• Free of known chronic disease and any medication (any medication within 30 days prior to the inclusion visit).

• Non-pathological ECG.

• Heart rate between 50 and 80 beats per minute rest.

• Complete Blood Count (CBC) with no significant anomaly 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.

• Serum electrolytes without clinically significant abnormalities in terms of the investigator.

• Fasting plasma glucose less than 1.1 g / l.

• HbA1c within the normal range (4-6%).

• Good peripheral vein (forearm and back of the hand).

• Agreement to participate in the establishment of a serum bank.

• Sedentary or practicing occasional physical activity.

• Ability to sign informed consent.

• Affiliation to a social security scheme.

Exclusion Criteria:

• 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"

• Repeated a QTc interval> 450 ms measurement

• Risk factor: 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/jour 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> 10 cig / day and can not be interrupted for 24 hours.

• Subject exclusion period of another protocol.

Related Conditions & MeSH terms

• Healthy
• Insulin Resistance

Intervention

Drug:
• Apelin
An apelin clamp in which an apelin infusion will be administered
• Placebo
A clamp reference during which a placebo solution (saline solution) will be administered

Locations

Country	Name	City	State
France	University Hospital of Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

References & Publications (1)

Gourdy P, Cazals L, Thalamas C, Sommet A, Calvas F, Galitzky M, Vinel C, Dray C, Hanaire H, Castan-Laurell I, Valet P. Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic-euglycaemic clamp. Diabetes Obes Metab. 20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of glucose infusion	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.	The last 30 minutes of a hyperinsulinemic euglycemic clamp
Secondary	Calculation of the index of insulin sensitivity (Si)		During 240 minutes at visits 2 and 3
Secondary	Changes in the measurement of systolic blood pressure during each clamp		During 240 minutes at visits 2 and 3
Secondary	Changes in the measurement of diastolic blood pressure during each clamp		During 240 minutes at visits 2 and 3
Secondary	Changes in heart rate measurement during each clamp		During 240 minutes at visits 2 and 3
Secondary	Changes in ECG during each clamp		During 240 minutes at visits 2 and 3
Secondary	Clinical signs of intolerance / allergy / toxicity at visit 2,3 and 4		During 240 minutes at visits 2 and 3
Secondary	Determination of plasma insulin at all sampling		During 240 minutes at visits 2 and 3
Secondary	Determination of plasma glucagon at all sampling times		During 240 minutes at visits 2 and 3
Secondary	Determination of plasma apelin at all sampling times		During 240 minutes at visits 2 and 3
Secondary	Determination of plasma leptin at all sampling times		During 240 minutes at visits 2 and 3
Secondary	Determination of plasma adiponectin at all sampling times		During 240 minutes at visits 2 and 3