Effect of GLP-1 on Angiogenesis (ANGIOSAFE 1)

June 14, 2021 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France, 13005
        • Nutrition department, pole ENDO - Assistance Publique Hôpitaux Marseille

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1: Liraglutide
Liraglutide 1,2 mg once daily subcutaneous injection for 1 month (4 weeks)
Drug: Liraglutide
Active Comparator: 2: Add on oral antidiabetic medication
Metformin or sulfonylurea depending on monotherapy
Drug: Metformin or sulfonylurea

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Difference of ANGPTL4 concentration at 4 weeks of treatment from baseline in Liraglutide and control group
Time Frame: At 1 month
At 1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
4 weeks
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
4 weeks
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 weeks
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
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Bénédicte GABORIT, MD, PhD, Assistance Publique - Hopitaux de Marseille

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2016

Primary Completion (Actual)

August 8, 2017

Study Completion (Actual)

May 28, 2021

Study Registration Dates

First Submitted

February 15, 2016

First Submitted That Met QC Criteria

February 18, 2016

First Posted (Estimate)

February 19, 2016

Study Record Updates

Last Update Posted (Actual)

June 15, 2021

Last Update Submitted That Met QC Criteria

June 14, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P140710
  • 2015-002930-35 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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