The Physiological Effects of Human Ether-a-go-go-Related Gene (hERG)Blockade on Metabolism

Summary

The human ether-a-go-go-related gene HERG (encoding Kv11.1 potassium channels) is expressed in different parts of the body including the heart, pancreas and intestines. In the heart, Kv11.1 channels play a role in ending depolarization by causing repolarization. Loss-of-function mutations of HERG cause long QT syndrome, a condition of elongated QT interval that can lead to ventricular tachycardia, syncope and sudden death. Kv11.1 channels are also found in pancreatic α- and β-cells and intestinal L-cells, where they seem to play a role in the secretion of insulin, glucagon and Glucagon-Like Peptide-1 (GLP-1). Carriers of loss-of-function mutations in the HERG gene have showed increased insulin and incretin responses after glucose ingestion and decreased fasting levels of glucagon compared to matched control persons. Blockade of Kv11.1 has shown to augment glucose dependent insulin secretion and decrease low-glucose stimulated glucagon secretion in isolated α- and β- cells. The investigators of this study hypothesize that a blockade of Kv11.1 channels will increase incretin and β cell function and decrease α cell function and thus lead to lower glucose levels in humans after glucose intake. To investigate this, The investigators of this study will perform a randomized, cross sectional study of up to 40 healthy study participants who will serve as their own controls. The study participants will undergo two 6-hours oral glucose tolerance tests, one after intake of a known Kv11.1 blocker (moxifloxacin) and one control oral glucose tolerance test after intake of placebo. Prior to both tests the study participants will wear a continuous glucose monitor and on the day of the tests they will fill out a glucose questionnaire. Investigation of the physiological role of HERG in metabolism may provide a better insight on metabolic regulation.

Conditions

• Long QT Syndrome
• Hypoglycemia

Interventions

DRUG

Moxifloxacin

Moxifloxacin is solely used to cause a known and for the drug well documented effect, namely blockade of the Kv11.1 channel.

DRUG

Placebo

Placebo

Sponsors & Collaborators

• Signe Torekov

  lead OTHER

Principal Investigators

• Signe S. Torekov, MSc, PhD · University of Copenhagen

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

20 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-01-28

Primary Completion

2019-08-19

Completion

2020-03-09

Countries

• Denmark

Study Locations