Effect of GLP-1 on Angiogenesis

Type 2 Diabetes Clinical Trial

— ANGIOSAFE 1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02686177
• Other study ID #: P140710
• Secondary ID: 2015-002930-35
• Status: Completed
• Phase: Phase 4
• Start date: May 18, 2016
• Est. completion date: May 28, 2021

Study information

• Verified date: June 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: May 28, 2021
• Est. primary completion date: August 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Liraglutide

• Metformin or sulfonylurea

Locations

Country	Name	City	State
France	Nutrition department, pole ENDO - Assistance Publique Hôpitaux Marseille	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference of ANGPTL4 concentration at 4 weeks of treatment from baseline in Liraglutide and control group		At 1 month
Secondary	Difference of ANGPT2 concentration at 4 weeks of treatment from baseline in Liraglutide and control group	We will use commercial ANGPT2 commercial ELISA assays	4 weeks
Secondary	Difference of endothelial circulating progenitor cells (CD34+KDR+) concentration at 4 weeks of treatment from baseline in Liraglutide and control group	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
Secondary	Difference of AngiomiR-126 expression at 4 weeks of treatment from baseline in Liraglutide and control group	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
Secondary	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)	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