Effect of Apelin on Insulin Sensitivity: Proof of Concept in Healthy Volunteers

NCT02033473 | Completed Phase 1 DMC

• 2 other identifiers: 13 182 03HAO 2013
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The (PYR1)-apelin-13 is an endogenous peptide discovered relatively recently (1998). The apelin and its receptor, which is named apj, are expressed in many tissues including sensitive to the action of insulin, such as skeletal muscle, adipose tissue and heart tissue. Recent work by the team of Prof. P.Valet (INSERM U1048, Toulouse) opened a new field of investigation, demonstrating for the first time in mouse models that apelin exerts a glucose-regulating in vivo action. The investigators propose a translational clinical research project whose goal is to provide the proof of concept of the favorable influence of apelin on insulin sensitivity in humans.

Conditions

Healthy

Keywords

Apelin; insulin; volunteers

Outcome Measures

Primary Outcomes (1)

• Rate of glucose infusion

  Measuring the difference between the rate of glucose infusion measured in the last 30 minutes of a hyperinsulinemic euglycemic clamp in the presence of a continuous infusion (PYR1)-apelin-13 infusion rate of glucose measured in the same conditions in the presence of a continuous infusion of placebo.

  The last 30 minutes of a hyperinsulinemic euglycemic clamp

Secondary Outcomes (11)

• Calculation of the index of insulin sensitivity (Si)

  During 240 minutes at visits 2 and 3

• Changes in the measurement of systolic blood pressure during each clamp

  During 240 minutes at visits 2 and 3

• Changes in the measurement of diastolic blood pressure during each clamp

  During 240 minutes at visits 2 and 3

• Changes in heart rate measurement during each clamp

  During 240 minutes at visits 2 and 3

• Changes in ECG during each clamp

  During 240 minutes at visits 2 and 3

Study Arms (2)

Apelin

EXPERIMENTAL

An apelin clamp in which an apelin infusion will be administered prior to reference clamp

Drug: Apelin; Drug: Placebo

Placebo

PLACEBO COMPARATOR

A clamp reference during which a placebo solution (saline solution) will be administered prior to apelin clamp

Drug: Apelin; Drug: Placebo

Interventions

Apelin DRUG

An apelin clamp in which an apelin infusion will be administered

Apelin; Placebo

Placebo DRUG

A clamp reference during which a placebo solution (saline solution) will be administered

Apelin; Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men aged 18 to 40 years.
• BMI between 25 and 30 kg / cm ² (excluding terminals).
• Non-pathological ECG.
• Heart rate between 50 and 80 beats per minute rest.
• Complete Blood Count (CBC) with no significant anomaly 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.
• Serum electrolytes without clinically significant abnormalities in terms of the investigator.
• Fasting plasma glucose less than 1.1 g / l.
• HbA1c within the normal range (4-6%).
• Good peripheral vein (forearm and back of the hand).
• Agreement to participate in the establishment of a serum bank.
• Sedentary or practicing occasional physical activity.
• Ability to sign informed consent.
• Affiliation to a social security scheme.

You may not qualify if:

• Risk factor, treatment or ECG as recommended by International Conference on Harmonization E14 (ICH E14) "Clinical Evaluation of QT / corrected QT interval (QTc Interval= Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs"
• Repeated a QTc interval\> 450 ms measurement
• Risk factor: 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/jour 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\> 10 cig / day and can not be interrupted for 24 hours.

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

University Hospital of Toulouse

Toulouse, 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

Insulin Resistance

Interventions

Apelin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Pierre GOURDY, Md, PhD

  University Hospital of Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: January 10, 2014
• Study Start: January 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: July 12, 2019

Record last verified: 2019-07

Locations

FR (1)