Clinical trial NCT02724566: Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers
Official title: Influence of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Keywords: Type 2 diabetic volunteers
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Société Francophone du Diabète
First posted: 2016-03-31
Enrollment: 9
Sex: MALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Delta between Glucose Infusion Rate
timeFrame: 240 minutes
Secondary outcomes:
measure: Measure of M-value (a glucose physiological parameter)
timeFrame: 240 minutes
measure: systolic blood pressure and diastolic blood pressure
timeFrame: 240 minutes
measure: heart rate
timeFrame: 240 minutes
measure: Measure of QTc interval with electrocardiogram examination
timeFrame: 240 minutes
measure: Clinic sign of apelin intolerance
timeFrame: 240 minutes
measure: Dosage of plasma proteins
timeFrame: 240 minutes
measure: Clinic sign of apelin allergy
timeFrame: 240 minutes
measure: Clinic sign of apelin toxicity
timeFrame: 240 minutes
Other outcomes:
Locations:
city: Toulouse
country: France
facility: University Hospitals of Toulouse (Rangueil)
state: Midi-Pyrénées
Study officials:
affiliation: University Hospital, Toulouse
name: Pierre Gourdy, PhD
role: PRINCIPAL_INVESTIGATOR
References: