Skip to main content
OpenTrials
Completed

NCT Number: NCT02686177

Effect of GLP-1 on Angiogenesis

GLP-1 receptor agonists are introduced in the treatment of type 2 Diabetes (T2D) and their efficacy is documented. However, safety aspects are also important to evaluate with respect to micro and macrovascular complications associated with T2D. Few studies have properly addressed the role of GLP-1-based therapies in regulating vascular integrity and angiogenesis. The study evaluate the impact of one-month treatment Liraglutide on both ANGPT2 and ANGLPT4 levels and endothelial circulating progenitor cells, angiogenesis biomarkers in type 2 diabetic patients.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Nutrition department, pole ENDO - Assistance Publique Hôpitaux Marseille

Marseille, 13005, France

About this study

GLP-1 receptor agonists are introduced in the treatment of type 2 Diabetes (T2D) and their efficacy is documented. Beside their therapeutic benefits, direct cardiovascular effects have also been reported. However, safety aspects are also important to evaluate with respect to micro and macrovascular complications associated with T2D. T2D patients treated with GLP-1 analogs may suffer from microvascular complications such as macular oedema and proliferative retinopathy, characterized by excessive retinal angiogenesis. Few studies have properly addressed the role of GLP-1-based therapies in regulating vascular integrity and angiogenesis. The role of GLP-1 on endothelial cell (EC) growth, EC integrity and angiogenesis thus needs to be characterized. Our aim is to provide the proof of concept that agonists of GLP-1 regulate angiogenesis in humans and identify the underlying mechanisms. The present project is the translational part of the ANR Angiosafe-T2D, regarding clinical safety aspects of GLP-1 receptor agonists (namely Liraglutide) on angiogenesis.

The study evaluate the impact of one-month treatment Liraglutide on both ANGPT2 and ANGLPT4 levels and endothelial circulating progenitor cells, angiogenesis biomarkers in type 2 diabetic patients.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Type 2 diabetic patients (ADA criteria)
  • Age > 18 years
  • Obesity (BMI >= 25 kg/m2)
  • HbA1c > 6.5 %
  • Treatment with Metformin and/or secretagogues
  • Effective contraception (women)

Exclusion criteria

  • Treatment with Exenatide, Liraglutide or other incretinergic regimen (<1 month before recruitment)
  • Type 1 diabetes
  • acute disease or infection
  • chronic renal failure (MDRD eGFR≤50 mL/min)
  • recent cardiovascular event or surgery (<3 months)
  • pancreatitis history
  • anti-VEGF treatment
  • untreated cancer
  • immunological disorders
  • pregnancy and lactation
  • Vulnerable people : deprivation of Liberty safeguards
  • hypersensitivity to the active substance or to any of the excipients of the investigational drug
  • diabetic ketoacidosis
  • heart failure stage 3 or 4 (NYHA III-IV)
  • Hepatic insufficiency
  • inflammatory bowel disease and gastroparesis
  • No affiliation to the social security

Treatment and study plan

liraglutide

Drug

Metformin or sulfonylurea

Drug

Primary outcomes

  1. Difference of ANGPTL4 concentration at 4 weeks of treatment from baseline in Liraglutide and control group

    Time frame: At 1 month

Secondary outcomes

  1. Difference of ANGPT2 concentration at 4 weeks of treatment from baseline in Liraglutide and control group

    Time frame: 4 weeks

    We will use commercial ANGPT2 commercial ELISA assays

  2. Difference of endothelial circulating progenitor cells (CD34+KDR+) concentration at 4 weeks of treatment from baseline in Liraglutide and control group

    Time frame: 4 weeks

    Circulating progenitor cells (EPCs) will be quantified using flow cytometry before and after one month treatment GLP-1 receptor agonist or reference treatment (control group). Briefly, after erythrocyte lysis, peripheral blood will be stained with 10µL fluorescein isothiocyanate-conjugated anti-human CD34 mAb (Becton Dickinson), 10µL phycoethrin-conjugated anti-human KDR mAb (R&D Systems), and 10µL allophycocyanin-conjugated anti-CD133 mAb (Miltenyi Biotech). The frequency of CD34+ cells, CD34+ KDR+ cells before and after GLP-1R agonist or control treatment will be determined by a two-dimensional side-scatter fluorescence dot plot analysis after appropriate gating using blood samples from above-stated recruited patients

  3. Difference of AngiomiR-126 expression at 4 weeks of treatment from baseline in Liraglutide and control group

    Time frame: 4 weeks

    AngiomiR-126 will be extracted from the fresh isolated cells using the miRNeasy Mini Kit (Qiagen) microRNA expression levels will be compared between type 2 diabetic subjects, before and after one-month GLP-1R agonist treatment and in the control group

  4. Difference of Circulating soluble adhesion molecules as endothelial activation markers: ICAM-1 and VCAM-1 concentration at 4 weeks of treatment from baseline (Liraglutide versus control group)

    Time frame: 4 weeks

    The measurement of circulating soluble adhesion molecules as endothelial activation markers: ICAM-1 and VCAM-1 will be done with ELISA commercial assays

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

Effect of GLP-1 on Angiogenesis, Angiosafe Type 2 Diabetes Study 1

Acronym: ANGIOSAFE 1

Important dates

Study start
2016
Primary completion
2017
Study completion
2021
First posted
Feb 19, 2016
Registry last updated
Jun 15, 2021

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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.