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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Apelin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • University Hospital of Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Pierre GOURDY, Md, PhD, University Hospital of Toulouse

Publications and helpful links

General Publications

• 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. 2018 Jan;20(1):157-164. doi: 10.1111/dom.13055. Epub 2017 Aug 10.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: December 12, 2013
• First Submitted That Met QC Criteria: January 9, 2014
• First Posted (Estimate): January 10, 2014

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: volunteers; insulin; Apelin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 13 182 03; HAO 2013 (Other Identifier: Hors Appel d'Offres)