The Impact of Glucose Lowering Therapies on Circulating Endothelial Progenitor Cells and Its Mobilising Factor Stromal Derived Factor-1α in Patients With Type 2 Diabetes

NCT02694575 | Completed DMC

• 1 other identifier: 0483
• Study Type: observational
• Target: 241
• Locations: 1 country
• Sites: 1

Brief Summary

This is a cross-sectional observational study aiming to examine and compare the impact of incretin based therapies i.e. dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, on endothelial progenitor cells (EPCs) and its mobilising factor, stromal derived factor-1 α (SDF-1 α), in patients with type 2 diabetes mellitus (T2DM) who are well established on those treatments. EPCs provide vascular protection by means of endothelial repair and neogenesis. This endothelial protective effect may potentially benefit patients affected by micro or macrovascular complications arising from vascular injury e.g. cardiovascular disease in T2DM. The study is of particular interest as a small study has shown an increase in level of circulating EPC in patients treated with DPP-4 inhibitors, thought to be mediated via the up regulation of its mobilising factor SDF-1 α.

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• EPC

  The measure of number of circulating Endothelial Progenitor Cells (EPCs) (EPC/μl)

  Single sample analysis - no time frame

Secondary Outcomes (13)

• SDF 1-α (Stromal derived factor-1α)

  Single sample analysis - no time frame

• Glucagon-like peptide 1 (GLP-1)

  Single sample analysis - no time frame

• Dipeptidyl peptidase 4 (DDP-4)

  Single sample analysis - no time frame

• C-reactive protein

  Single sample analysis - no time frame

• Nitric oxide (NO)

  Single sample analysis - no time frame

Study Arms (3)

Other

Other - currently on other treatment (i.e., non-incretin based therapies)

GLP-1

Currently on GLP-1 analogue therapy

DPP-4

Currently on DPP-4 inhibitor therapy

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Male and female patients aged between 35 and 70 years of age (inclusve) who have established Type 2 Diabetes mellitus (T2DM) and who have been receiving either (a) DPP-4 inhibitors, (b) GLP-1 analogues, or (c) non-incretin based treatments for at least 3 months (or more).

You may qualify if:

• Capacity to provide informed consent before any study-related activities
• Individuals aged 35-70 years inclusive
• Both male and female
• Diagnosed with T2DM for at least 1 year
• On DPP4-inhibitor, GLP-1 analogue or non-incretin agent for at least 3 months regardless of their background treatment
• White European or South Asian ethnicity (to increase the comparability of treatment groups)

You may not qualify if:

• Type 1 diabetes
• Individuals \<35 or \>70 years of age
• Prescribed thiazolidinediones or sodium-glucose co-transporter-2 (SGLT-2) inhibitors within the last 3 months
• Any form of terminal illness

Sponsors & Collaborators

• University of Leicester: lead
• University Hospitals, Leicester: collaborator

Study Sites (1)

Leicester Diabetes Centre

Leicester, Leicestershire, LE5 4PW, United Kingdom

Location

Related Publications (24)

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• Ahren B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab. 2004 May;89(5):2078-84. doi: 10.1210/jc.2003-031907.

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral Blood Mononuclear Cells (PBMCs) for subsequent EPC quantification: PBMCs will be isolated from venous blood collected into a 9.7ml sodium heparin blood tube. EPCs will be quantified as cells showing dual positivity for the cell surface / transmembrane markers: CD24 and KDR (Kinase Insert Domain Receptor). SDF-1α analysis and the analysis of biomarkers associated with the prevalence of circulating EPCs will be measured using sandwich ELISA and multi-array ELISA technology in-line with manufacturer protocols. Analysis of endogenous DPP4 will be assayed using a commercial colorimetric assay; again manufacturer protocols will be followed. Biomarker and DPP4 analysis will be carried out in one batch on stored sodium heparin plasma samples.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Melanie J Davies, MBBS MD

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: February 29, 2016
• Study Start: March 1, 2015
• Primary Completion: April 12, 2017
• Study Completion: August 31, 2018
• Last Updated: January 30, 2020

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)