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

Influence of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: apelin; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Midi-Pyrénées
    • Toulouse, Midi-Pyrénées, France, 31059
      • University Hospitals of Toulouse (Rangueil)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Apelin then Placebo; 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	Drug: apelin; 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).; Other Names: [pyr1]-apelin-13 infusion; Drug: placebo; 2 hours continuous infusion of placebo (vehicle alone) to compare with 2 hours infusion of apelin
Other: Placebo then Apelin; 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	Drug: apelin; 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).; Other Names: [pyr1]-apelin-13 infusion; Drug: placebo; 2 hours continuous infusion of placebo (vehicle alone) to compare with 2 hours infusion of apelin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	240 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	240 minutes
systolic blood pressure and diastolic blood pressure		240 minutes
heart rate		240 minutes
Measure of QTc interval with electrocardiogram examination		240 minutes
Clinic sign of apelin intolerance		240 minutes
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	240 minutes
Clinic sign of apelin allergy	Modification in physiological parameters	240 minutes
Clinic sign of apelin toxicity	Modification in physiological parameters	240 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Société Francophone du Diabète
• Investigators: Principal Investigator: Pierre Gourdy, PhD, University Hospital, 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 (Actual): May 1, 2016
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: March 24, 2016
• First Posted (Estimated): March 31, 2016

Study Record Updates

• Last Update Posted (Estimated): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Type 2 diabetic volunteers
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus; Peptides; Amino Acids, Peptides, and Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Apelin
• Other Study ID Numbers: 15 7783 03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO