The Physiological Effects of Human Ether-a-go-go-Related Gene (hERG)Blockade on Metabolism
Status:
Enrolling by invitation
Trial end date:
2025-12-31
Target enrollment:
Participant gender:
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.
Phase:
N/A
Details
Lead Sponsor:
Signe Torekov
Treatments:
Moxifloxacin Norgestimate, ethinyl estradiol drug combination