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

Study Overview
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Brief Summary
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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.

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

Conditions
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Insulin Resistance

Intervention / Treatment
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* Drug: Placebo
* Drug: Nicorandil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy subjects<br>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<br>* placebo tablet<br>Drug: Nicorandil<br>* 20 mg nicorandil (Ikorel, Sanofi Winthrop Industrie; NIC)<br>|
| Experimental: Insulin resistant<br>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<br>* placebo tablet<br>Drug: Nicorandil<br>* 20 mg nicorandil (Ikorel, Sanofi Winthrop Industrie; NIC)<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skeletal muscle, muscle fatigue, ion handling