Incretin and KATP Channels

Effects of KATP Channel Blockers on GLP-1 and Its Analogues' Mediated Microvascular Function

This study aims to examine the involvement of KATP channels on the microvascular actions of the incretin GLP-1 and its analogues in healthy individuals and to determine whether the acute oral administration of different KATP channel blockers which are oral medications for Type 2 diabetes such as Glibenclamide and Glimepiride differentially modulate the microvascular responses in these individuals.

Study Overview

• Status: Terminated
• Conditions: Healthy Subjects
• Intervention / Treatment: Other: Intradermal injections of GLP-1 and its analogues

Detailed Description

In addition to the glucose lowering effect, incretin based therapies have also an effect on the vascular system. Previous animal work and initial human studies suggest that incretins may be cardioprotective and act as vasodilators through opening of KATP channels.

Initial evidence suggests that beneficial vascular effects of incretin modifying agents may be nullified by the co-current treatment of the sulfonylurea (SU) drug glibenclamide. The investigators hypothesis is that the GLP-1 and SUs may have conflicting effects on the KATP channels and thus vascular function.

Interestingly the vascular actions of GLP-1 were not modified by a different treatment SUs called glimepiride, thereby raising the possibility that SUs differentially modulating the vascular actions of GLP-1 though this remains controversial.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Exeter, United Kingdom, EX25DW
    • Royal Devon and Exeter NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI ≤ 25 kg/m2

Exclusion Criteria:

• current or past history of diabetes (HbA1C more or equal 45mmol/mol)
• history of postprandial hypoglycaemia and dumping syndrome
• established cardiovascular disease
• established cerebrovascular disease
• blood pressure ≥ 140/85 mmHg
• Raynaud's disease
• severe impairment of renalhepatic, thyroid or adrenocortical function
• current treatment with any anti-hypertensive treatment
• lipid lowering therapy or systemic steroids
• lactation, pregnancy
• established vascular disease
• bariatric surgery
• significant weight change within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glimepiride; 4mg of Glimepiride once only before vascular testing and intradermal injections of GLP-1 and its analogues	Other: Intradermal injections of GLP-1 and its analogues; native GLP-1,Exenatide (Byetta)and Liraglutide (Victoza) will be microinjected at the same visit in no particular order in all study arms; Other Names: microinjection of GLP-1 (native GLP-1); and its analogues such as Exenatide(Byetta); and Liraglutide (Victoza)
Placebo Comparator: Placebo tablet; Placebo tablet is given in the morning of the intradermal injections of GLP-1 and its analogues	Other: Intradermal injections of GLP-1 and its analogues; native GLP-1,Exenatide (Byetta)and Liraglutide (Victoza) will be microinjected at the same visit in no particular order in all study arms; Other Names: microinjection of GLP-1 (native GLP-1); and its analogues such as Exenatide(Byetta); and Liraglutide (Victoza)
Active Comparator: Glyburide; 10mg of Glyburide before study visit and intradermal injections of GLP-1 and its analogues	Other: Intradermal injections of GLP-1 and its analogues; native GLP-1,Exenatide (Byetta)and Liraglutide (Victoza) will be microinjected at the same visit in no particular order in all study arms; Other Names: microinjection of GLP-1 (native GLP-1); and its analogues such as Exenatide(Byetta); and Liraglutide (Victoza)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in skin blood flow to GLP-1 and its analogues	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	6 weeks

Collaborators and Investigators

• Sponsor: Katarina Kos
• Collaborators: University of Exeter
• Investigators: Principal Investigator: Katarina Kos, FRCP, PhD, University of Exeter

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: August 19, 2013
• First Submitted That Met QC Criteria: August 29, 2013
• First Posted (Estimate): September 4, 2013

Study Record Updates

• Last Update Posted (Actual): February 17, 2017
• Last Update Submitted That Met QC Criteria: February 16, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Incretins, KATP channels, intradermal injection
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Liraglutide; Glucagon; Exenatide; Glucagon-Like Peptide 1
• Other Study ID Numbers: 2Myo2013; 1308823 (Registry Identifier: Trust Research and Development); 13/SW/0010 (Other Identifier: REC)