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: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Signe Torekov
• Treatments: Moxifloxacin; Norgestimate, ethinyl estradiol drug combination

Criteria

Inclusion Criteria:

• Healthy men and women

• Age ≥20 and ≤40 years

• BMI ≥18,5 and ≤27,5

Exclusion Criteria:

• Chronic diseases (cardiac, metabolic, liver) including a family history of congenital Long QT syndrome.

• QTc values >440 ms (men) and >450 ms (women)

• Clinical important and/or symptomatic bradycardia

• Regular medication (contraceptive pills allowed)

• Pregnancy and breastfeeding