The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity

Diabetes Clinical Trial

Official title:

The Effect of Antecedent Hypoglycaemia on β2-adrenergic Sensitivity in Subjects With Homozygous Arg16 and gly16 Polymorphism of the β2-adrenergic Receptor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00160056
• Other study ID #: HB2-001
• Status: Completed
• Phase: N/A
• First received: September 9, 2005
• Last updated: May 8, 2015
• Start date: April 2005
• Est. completion date: April 2009

Study information

• Verified date: May 2015
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Hypoglycaemia unawareness is a common complication in patients with type 1 diabetes and with insulin-treated type 2 diabetes of long duration. The loss of autonomic symptoms to hypoglycemia does not solely depend on loss of adrenaline responses.Differences in sensitivity to catecholamines may also be involved.

Reconciling the data on β2-adrenergic receptor polymorphism to those on loss of β-adrenergic sensitivity in diabetic patients with hypoglycemia unawareness, we hypothesize that hypoglycemia unawareness is at least partly the result of desensitization of the β2-adrenergic receptor and that patients who are homozygous for arginine at codon 16 are particularly susceptible for this desensitization process, whereas patients who are homozygous for glycine at codon 16 are resistant for desensitization.

Objectives

1. To determine whether, and if so to what extent, antecedent hypoglycemia reduces β2-adrenergic sensitivity in healthy subjects with Arg16 homozygosity.

2. To investigate whether or not healthy subjects with Gly16 homozygosity are resistant to desensitization

3. To confirm that antecedent hypoglycemia reduces the heart rate response to isoproterenol and to assess to what extent this reduced response is mediated by impairments in baroreflex sensitivity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Informed consent

• Homozygous for Arginine at codon 16 or homozygous Gly at codon 16

• No regular usage of medication other than oral contraceptives

Exclusion Criteria:

• History of cerebrovascular, cardiovascular, or peripheral vascular disease

• Smoking

• Alcohol usage of more than 10 units per week

• Inability to abstain from xanthine-derivatives (coffee, tea, cola, chocolate, cacao) or alcohol for 2 days

• BMI above 30 kg/m2

• Participation to any other trial in the preceding 3 months

• Ongoing disease of any kind

• Pregnancy

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Diabetes
• Hypoglycemia
• Hypoglycemia Unawareness
• Unconsciousness

Intervention

Procedure:
• Hypoglycemia

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands,