Incretin and KATP Channels

Katarina Kos

Status: Terminated

Conditions: Healthy Subjects

Treatments: Other: Intradermal injections of GLP-1 and its analogues

Study type: Interventional

Funder types: Other

Identifiers

NCT01934816

13/SW/0010 (Other Identifier)

2Myo2013

1308823 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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2 participants in 3 patient groups, including a placebo group

Glimepiride

Experimental group

Description:

4mg of Glimepiride once only before vascular testing and intradermal injections of GLP-1 and its analogues

Treatment:

Other: Intradermal injections of GLP-1 and its analogues

Placebo tablet

Placebo Comparator group

Description:

Placebo tablet is given in the morning of the intradermal injections of GLP-1 and its analogues

Treatment:

Other: Intradermal injections of GLP-1 and its analogues

Glyburide

Active Comparator group

Description:

10mg of Glyburide before study visit and intradermal injections of GLP-1 and its analogues

Treatment:

Other: Intradermal injections of GLP-1 and its analogues