GLP-1 and Microvascular Function in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— GLP-1ADDS  

Official title:

Does Glucagon-like Polypeptide 1 Improve Vascular Function and Inflammation?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01740921
• Other study ID #: 066
• Secondary ID: 10/H0106/29
• Status: Completed
• Phase: N/A
• First received: November 22, 2012
• Last updated: February 16, 2017
• Start date: January 2011
• Est. completion date: February 2016

Study information

• Verified date: February 2017
• Source: Royal Devon and Exeter NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Some gut hormones, called incretins, stimulate insulin production in order to control sugar levels but also activate brain centres and signal to stop eating. Current administration of incretin-based therapies mimicking these gut hormones is by subcutaneous (just under the skin) injection and has been routinely available for diabetic patients for more than 4 years. It is an effective treatment for the lowering of blood glucose with an average weight loss of about 3-4kg.Recent evidence, from animal studies and limited human studies, suggests that incretins based treatments may also have beneficial effects on blood vessel function. However, it is not known whether this effect is by direct action on the blood vessel independent of an improvement of latent inflammation which is typically associated with weight loss or an anti-inflammatory effect of the incretin treatment itself. The aim of this study is to determine whether the incretin-based diabetes treatment with the GLP-1 (Glucagon-like peptide 1) analogue Liraglutide (also known as Victoza), which mimics the actions of incretins, improves blood vessel function in individuals with type 2 diabetes. It will determine whether the improvement in blood vessel function is independent of the effect of weight loss and changes in inflammation. This by the study of vascular function before and after 4 months of Victoza treatment in subjects with Type 2 diabetes in comparison with 1) participants randomized to hypo-caloric diet to achieve a similar weight loss than with Victoza and 2) participants randomized to treatment with once daily aspirin. Comprehensive assessment of blood vessel function, body fat distribution and metabolic profile at baseline and at the end of the treatment phase will be combined with assessments of inflammation markers in blood and in fat tissue biopsies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: February 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes and an HbA1C between 7-8.5% on a stable dose of sulphonylurea and/or metformin

Exclusion Criteria:

• use of insulin

• corticosteroids

• contraceptives, tamoxifen

• methotrexate

• DPP-IV inhibitors

• pregnancy

• lactation

• endocrine disorders

• acute MI or cerebrovascular disease

• Raynaud's disease or connective tissue disease

• current or previous history of malignancy

• subjects treated with ergotamine derivatives

• unstable blood pressure for the last 3 months

• current treatment with warfarin

• subjects on any anti-inflammatory or anti-platelet agents

• history of any bleeding disorders and GI bleeds.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Liraglutide
Administered once daily

Other:
• diet
reduction of caloric intake to promote weight loss

Drug:
• Aspirin
300mg of Aspirin per day

Locations

Country	Name	City	State
United Kingdom	Peninsula Clinical Research Facility	Exeter

Sponsors (2)

Lead Sponsor	Collaborator
Royal Devon and Exeter NHS Foundation Trust	University of Exeter

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Pastel E, McCulloch LJ, Ward R, Joshi S, Gooding KM, Shore AC, Kos K. GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction. Clin Sci (Lond). 2017 Jan 3. pii: CS20160803. doi: 10.1042/CS20160803. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	change of baseline clot structure at 4 months	rigidity and elasticity of clot structure	baseline and 4 months
Other	change of baseline adipose tissue inflammation at 4 months	adipose tissue biopsies will be analysed for gene expression and protein content of inflammatory cytokines	baseline and 4 months
Primary	change of baseline skin maximum hyperaemia at 4 months	laser doppler fluximetry	baseline and 4 months
Secondary	change of baseline peripheral arterial tone at 4 months	ITAMAR	baseline and 4 months
Secondary	change of baseline endothelial-dependent vasodilation at 4 months	iontophoresis	baseline and 4 months
Secondary	change of baseline capillary density at 4 months	capillaroscopy	baseline and 4 months