Regulation of KATP Channels and Na+/K+ ATPase in Relation to Fatigue Development

Regulation of KATP Channels and Na+/K+ ATPase in Relation to Fatigue Development in Healthy and Insulin Resistant Subjects

To investigate the role of ATP sensitive K+ potassium channels and the Na+/K+ pump in the development of fatigue in healthy and in insulin resistant subjects.

Study Overview

• Status: Completed
• Conditions: Insulin Resistance
• Intervention / Treatment: Drug: Placebo; Drug: Nicorandil

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Danmark
    • Copenhagen, Danmark, Denmark, 2100
      • University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Non smokers
• HbA1c <38 mmol/mol (<5.7%), HOMA-IR > 1.7 (insulin resistant)
• VO2max <40 ml/kg/min (insulin resistant), 45-55 ml/kg/m2 (healthy)
• BMI >26 kg/m2 (insulin resistant), 19-26 kg/m2 (healthy)

Exclusion Criteria:

• Use of antidiabetic medication or any other medication deemed to interfere with study outcomes
• Allergy towards Nicorandil
• Chronic disease other than type 2 diabetes deemed to interfere with study outcomes
• Excessive alcohol consumption (>14 units/week)
• Abnormal ECG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy subjects; Two experimental day where the effect of Nicorandil (20mg) or placebo will asses the function of the ATP sensitive potassium pumps role in the development of fatigue.	Drug: Placebo; placebo tablet; Drug: Nicorandil; 20 mg nicorandil (Ikorel, Sanofi Winthrop Industrie; NIC)
Experimental: Insulin resistant; Two experimental day where the effect of Nicorandil (20mg) or placebo will asses the function of the ATP sensitive potassium pumps role in the development of fatigue.	Drug: Placebo; placebo tablet; Drug: Nicorandil; 20 mg nicorandil (Ikorel, Sanofi Winthrop Industrie; NIC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular potassium concentration meassured with microdialysis	Interstitial potassium	Changes in potassium handling from the placebo experimental day compared to the experimental days with Nicorandil ingestion with 14 days between each experimental day. Timeframe pr. subject approx. 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance (time to exhaustion) during knee extensor exercise	Muscle exercise tolerance	Changes in performance during the placebo experimental day compared to the experimental days with Nicorandil ingestion with 14 days between each experimental day. Timeframe pr. subject approx. 6 weeks.

Collaborators and Investigators

• Sponsor: University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2018
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: December 13, 2018
• First Posted (Actual): December 14, 2018

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: muscle fatigue; skeletal muscle; ion handling
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Fatigue; Insulin Resistance; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Micronutrients; Vitamins; Vitamin B Complex; Nicorandil
• Other Study ID Numbers: NAK-KATP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No