GLP-1 and Microvascular Function in Type 2 Diabetes

NCT01740921 | Completed

• 2 other identifiers: 06610/H0106/29
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes

Keywords

GLP-1 analogues; microvascular; inflammation; fat tissue; clot structure

Outcome Measures

Primary Outcomes (1)

• change of baseline skin maximum hyperaemia at 4 months

  laser doppler fluximetry

  baseline and 4 months

Secondary Outcomes (3)

• change of baseline peripheral arterial tone at 4 months

  baseline and 4 months

• change of baseline endothelial-dependent vasodilation at 4 months

  baseline and 4 months

• change of baseline capillary density at 4 months

  baseline and 4 months

Other Outcomes (2)

• change of baseline clot structure at 4 months

  baseline and 4 months

• change of baseline adipose tissue inflammation at 4 months

  baseline and 4 months

Study Arms (3)

Liraglutide

ACTIVE COMPARATOR

Liraglutide (Victoza) daily injections

Drug: Liraglutide

diet

PLACEBO COMPARATOR

reduction in calorie intake

Other: diet

Aspirin

PLACEBO COMPARATOR

Aspirin 300mg once daily

Drug: Aspirin

Interventions

Liraglutide DRUG

Administered once daily

Also known as: Victoza, GLP-1 analogue

Liraglutide

diet OTHER

reduction of caloric intake to promote weight loss

Also known as: caloric restriction

diet

Aspirin DRUG

300mg of Aspirin per day

Aspirin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Royal Devon and Exeter NHS Foundation Trust: lead
• University of Exeter: collaborator

Study Sites (1)

Peninsula Clinical Research Facility

Exeter, EX2 5DW, United Kingdom

Location

Related 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 Mar 1;131(5):343-353. doi: 10.1042/CS20160803. Epub 2017 Jan 3.

  PMID: 28049736 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation

Interventions

Liraglutide; Diet; Caloric Restriction; Aspirin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Katarina Kos, MD,PhD

  University of Exeter

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer and Honorary Consultant Physician

Study Record Dates

• First Submitted: November 22, 2012
• First Posted: December 4, 2012
• Study Start: January 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2016
• Last Updated: February 17, 2017

Record last verified: 2017-02

Locations

GB (1)