Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

NCT02724566 | Completed Phase 1 DMC

• 1 other identifier: 15 7783 03
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes

Keywords

Type 2 diabetic volunteers

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Measure of M-value (a glucose physiological parameter)

  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

Study Arms (2)

Apelin then Placebo

OTHER

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; Drug: placebo

Placebo then Apelin

OTHER

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; Drug: placebo

Interventions

placebo DRUG

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

Apelin then Placebo; Placebo then Apelin

apelin DRUG

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).

Also known as: [pyr1]-apelin-13 infusion

Apelin then Placebo; Placebo then Apelin

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Secondary prevention of cardio-vascular disease
• 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.

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• Société Francophone du Diabète: collaborator

Study Sites (1)

University Hospitals of Toulouse (Rangueil)

Toulouse, Midi-Pyrénées, 31059, France

Location

Related Publications (1)

• 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.

  PMID: 28681996 RESULT

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Apelin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Pierre Gourdy, PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: March 31, 2016
• Study Start: May 1, 2016
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: December 10, 2025

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)