The Microvascular Function of GLP-1 and Its Analogues

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Royal Devon and Exeter NHS Foundation Trust
Sponsor:
Collaborator:
Diabetes UK
Information provided by (Responsible Party):
Katarina Kos, Royal Devon and Exeter NHS Foundation trust
ClinicalTrials.gov Identifier:
NCT01677104
First received: August 29, 2012
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

Incretins have become a successful drug target in the repertoire of medications used for the treatment of type 2 diabetes. However little is known about a potential benefit of GLP-1 on the vascular system in humans, independent of their glucose lowering actions and data are only derived from ex vivo studies in animals. Particularly little is known about clinically relevant benefits of GLP-1 and its analogues on the microvascular system of individuals with type 2 diabetes.

The vascular effect could be medicated by endogenous GLP-1 (9,36) amide, the breakdown product of GLP-1 (7,36) amide which has a low affinity for the GLP-1 receptor. The investigators hypothesis is that the co-administration of DPP-IV inhibitors will lack the beneficial effects of GLP-1 on the vascular system as GLP-1 (9,36) amide will not be produced by the body.

The study aims to examine the response of GLP-1 and its analogues on small blood vessels and examine the effect of the addition of DPP-IV inhibition in healthy lean individuals, obese individuals and subjects with Type 2 diabetes.


Condition Intervention
Type 2 Diabetes
Obesity
Drug: GLP-1
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: The Microvascular Function of GLP-1 and Its Analogues in Humans, in Vivo: the Role of DPP-IV Inhibition

Resource links provided by NLM:


Further study details as provided by Royal Devon and Exeter NHS Foundation Trust:

Primary Outcome Measures:
  • skin blood flow [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    skin blood flow will be assessed before and after microinjection of GLP-1 or its analogues and the injection site monitored and compared to sites injected with placebo


Estimated Enrollment: 63
Study Start Date: August 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: DPP-IV inhibitor
Linagliptin 5mg (Tradjenta) before microinjection of GLP-1 and its analogues
Drug: GLP-1
GLP-1 and its analogues will be compared with placebo with and without prior DPP-IV inhibition
Other Names:
  • native GLP-1(7,36)
  • Exenatide (Byetta)
  • Liraglutide (Vicotza)
Drug: Placebo
Other Name: placebo
Placebo Comparator: Placebo pill
One placebo tablet before microinjection
Drug: GLP-1
GLP-1 and its analogues will be compared with placebo with and without prior DPP-IV inhibition
Other Names:
  • native GLP-1(7,36)
  • Exenatide (Byetta)
  • Liraglutide (Vicotza)
Drug: Placebo
Other Name: placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Lean BMI ≤ 25.0 kg/m2
  • Obese BMI ≥30.0kg/m2
  • Non diabetic subjects and subjects with Type 2 diabetes on stable medication for at least 3 months

Exclusion Criteria:

  • cardiovascular disease
  • Raynaud's disease
  • current treatment with any anti-hypertensive
  • lipid lowering therapies
  • severe hepatic impairment
  • pregnancy and lactation
  • subjects with Type 2 diabetes on insulin therapy
  • subjects with Type 2 diabetes on sulphonylureas
  • subjects with Type 2 diabetes on incretin based therapies
  • subjects with Type 2 diabetes and peripheral vascular disease
  • subjects with Type 2 diabetes and history of advanced retinopathy
  • subjects with Type 2 diabetes and advanced nephropathy
  • subjects with Type 2 diabetes with uncontrolled diabetes (HbA1c > 8.5%)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01677104

Contacts
Contact: Katarina Kos, MD, PHD 01392406761 katarina.kos@pcmd.ac.uk
Contact: Kim Gooding, PhD 01392403081 kim.gooding@pcmd.ac.uk

Locations
United Kingdom
Diabetes and Vascular Center Recruiting
Exeter, United Kingdom, EX2 5AX
Contact: Kim Gooding, PhD    01392403081    kim.gooding@pcmd.ac.uk   
Sub-Investigator: Kim Gooding, PhD         
Principal Investigator: Angela Shore, PhD         
Sponsors and Collaborators
Katarina Kos
Diabetes UK
Investigators
Principal Investigator: Katarina Kos, MD, PHD Institue of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter
  More Information

No publications provided

Responsible Party: Katarina Kos, Consultant Physician and Senior Lecturer, Royal Devon and Exeter NHS Foundation trust
ClinicalTrials.gov Identifier: NCT01677104     History of Changes
Other Study ID Numbers: 11/SW/0195, 1204620
Study First Received: August 29, 2012
Last Updated: February 18, 2014
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Royal Devon and Exeter NHS Foundation Trust:
GLP-1
DPP-IV inhibitor
microcirculation
Exenatide
Liraglutide
Linagliptin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Liraglutide
Glucagon-Like Peptide 1
Glucagon
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014