NCT01677104

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
63

participants targeted

Target at P50-P75 for not_applicable type-2-diabetes

Timeline
Completed

Started Aug 2012

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2012

Completed
28 days until next milestone

First Submitted

Initial submission to the registry

August 29, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 31, 2012

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2014

Completed
Last Updated

April 13, 2017

Status Verified

April 1, 2017

Enrollment Period

1.9 years

First QC Date

August 29, 2012

Last Update Submit

April 12, 2017

Conditions

Type 2 DiabetesObesity

Keywords

GLP-1DPP-IV inhibitormicrocirculationExenatideLiraglutideLinagliptin

Outcome Measures

Primary Outcomes (1)

  • skin blood flow

    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

    3 hours

Study Arms (2)

DPP-IV inhibitor

ACTIVE COMPARATOR

Linagliptin 5mg (Tradjenta) before microinjection of GLP-1 and its analogues

Drug: GLP-1Drug: Placebo

Placebo pill

PLACEBO COMPARATOR

One placebo tablet before microinjection

Drug: GLP-1Drug: Placebo

Interventions

GLP-1DRUG

GLP-1 and its analogues will be compared with placebo with and without prior DPP-IV inhibition

Also known as: native GLP-1(7,36), Exenatide (Byetta), Liraglutide (Vicotza)
DPP-IV inhibitorPlacebo pill
PlaceboDRUG
DPP-IV inhibitorPlacebo pill

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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%)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Diabetes and Vascular Center

Exeter, EX2 5AX, United Kingdom

Location

Related Publications (1)

  • Aung MM, Slade K, Freeman LAR, Kos K, Whatmore JL, Shore AC, Gooding KM. Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes. Diabetologia. 2019 Sep;62(9):1701-1711. doi: 10.1007/s00125-019-4918-x. Epub 2019 Jun 16.

    PMID: 31203378DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Obesity

Interventions

Glucagon-Like Peptide 1ExenatideLiraglutide

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesOverweightOvernutritionNutrition DisordersBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like PeptidesProglucagonGastrointestinal HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPeptidesAmino Acids, Peptides, and ProteinsVenomsComplex MixturesToxins, BiologicalBiological Factors

Study Officials

  • Katarina Kos, MD, PHD

    Institue of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
DIAGNOSTIC
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Consultant Physician and Senior Lecturer

Study Record Dates

First Submitted

August 29, 2012

First Posted

August 31, 2012

Study Start

August 1, 2012

Primary Completion

July 1, 2014

Study Completion

July 1, 2014

Last Updated

April 13, 2017

Record last verified: 2017-04

Locations

GB(1)