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

Toulouse University Hospital

Status and phase: Completed; Phase 1

Conditions: Diabetes

Treatments: Drug: apelin; Drug: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02724566

15 7783 03

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 patients

Sex: Male

Ages: 40 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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9 participants in 2 patient groups

Apelin then Placebo

Other group

Description:

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

Treatment:

Drug: placebo

Drug: apelin

Placebo then Apelin

Other group

Description:

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

Treatment:

Drug: placebo

Drug: apelin