Effects of KATP Channel Blockers on GLP-1 and Its Analogues' Mediated Microvascular Function
Trial Snapshot
- Phase
- Not Applicable
- Status
- Terminated
- Sponsor
- Enrollment
- 2
- Locations
- 2
- Primary Endpoint
- Change in skin blood flow to GLP-1 and its analogues
Study Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Health Services Research
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Outcomes
Primary Outcomes
Change in skin blood flow to GLP-1 and its analogues
Time Frame: 6 weeks
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
Secondary Outcomes
No secondary outcomes reported
Investigators
Katarina Kos
Senior Lecturer
Royal Devon and Exeter NHS Foundation Trust