Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

Phase 1

Completed

• Conditions: Diabetes
• Interventions: Drug: apelin; Drug: placebo

• Registration Number: NCT02724566
• Lead Sponsor: University Hospital, Toulouse

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.

Study Timeline

• Study First Submitted: 2016-03-18
• Study First Submitted QC: 2016-03-24
• Study First Posted: 2016-03-31
• Study Start: 2016-05
• Primary Completion: 2017-04
• Study Completion: 2017-04
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-21
• Last Update Posted: 2017-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Apelin then Placebo	apelin	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
Apelin then Placebo	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
Placebo then Apelin	placebo	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
Placebo then Apelin	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

Primary Outcome Measures

Name	Time	Method
Delta between Glucose Infusion Rate	240 minutes	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).

Secondary Outcome Measures

Name	Time	Method
Clinic sign of apelin toxicity	240 minutes	Modification in physiological parameters
Measure of M-value (a glucose physiological parameter)	240 minutes	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).
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	240 minutes	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
Clinic sign of apelin allergy	240 minutes	Modification in physiological parameters

Trial Locations

Locations (1)

University Hospitals of Toulouse (Rangueil); 🇫🇷 Toulouse, Midi-Pyrénées, France