Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

Diabetes Clinical Trial

— APELINS-2  

Official title:

Influence of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02724566
• Other study ID #: 15 7783 03
• Status: Completed
• Phase: Phase 1
• First received: March 18, 2016
• Last updated: August 21, 2017
• Start date: May 2016
• Est. completion date: April 2017

Study information

• Verified date: August 2017
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes
• Insulin Resistance

Intervention

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).
• placebo
2 hours continuous infusion of placebo (vehicle alone) to compare with 2 hours infusion of apelin

Locations

Country	Name	City	State
France	University Hospitals of Toulouse (Rangueil)	Toulouse	Midi-Pyrénées

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Société Francophone du Diabète

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	systolic blood pressure and diastolic blood pressure		240 minutes
Secondary	heart rate		240 minutes
Secondary	Measure of QTc interval with electrocardiogram examination		240 minutes
Secondary	Clinic sign of apelin intolerance		240 minutes
Secondary	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
Secondary	Clinic sign of apelin allergy	Modification in physiological parameters	240 minutes
Secondary	Clinic sign of apelin toxicity	Modification in physiological parameters	240 minutes