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NCT Number: NCT02724566

Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

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.

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Key information

Age range

40 year–65 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

University Hospitals of Toulouse (Rangueil)

Toulouse, Midi-Pyrénées, 31059, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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).

Other names: [pyr1]-apelin-13 infusion

Placebo

Drug

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

Primary outcomes

  1. Delta between Glucose Infusion Rate

    Time frame: 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 outcomes

  1. Measure of M-value (a glucose physiological parameter)

    Time frame: 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).

  2. systolic blood pressure and diastolic blood pressure

    Time frame: 240 minutes

  3. heart rate

    Time frame: 240 minutes

  4. Measure of QTc interval with electrocardiogram examination

    Time frame: 240 minutes

  5. Clinic sign of apelin intolerance

    Time frame: 240 minutes

  6. Dosage of plasma proteins

    Time frame: 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

  7. Clinic sign of apelin allergy

    Time frame: 240 minutes

    Modification in physiological parameters

  8. Clinic sign of apelin toxicity

    Time frame: 240 minutes

    Modification in physiological parameters

Sponsors and collaborators

Lead sponsor

University Hospital, Toulouse

Other

Collaborators

  • Société Francophone du Diabète

Registry information

Official study title

Influence of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers

Acronym: APELINS-2

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Mar 31, 2016
Registry last updated
Dec 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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