Hypoxia and Exercise in the Elderly

Study Overview
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Brief Summary
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Ageing is the primary risk factor for most chronic diseases including type 2 diabetes mellitus. Sarcopenia and muscular mitochondrial dysfunction with aging are crucial mechanisms leading to decreased exercise tolerance and worsened insulin sensitivity. Thus, metabolic disease and frailty, which limits physical mobility as well as quality of life, share common cellular mechanisms. The investigators will test the hypothesis that a combination of normobaric hypoxia and exercise training elicits a synergistic effect on age-associated metabolic skeletal muscle dysfunction and the investigators will address the molecular mechanisms. In a randomized clinical study, the investigators will compare normoxic and hypoxic training conditions in elderly subjects. Outcome measures will focus on whole body insulin sensitivity and mitochondrial responses in skeletal muscle before and after the 8-week training intervention.

Official Title
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Hypoxia and Aerobic Exercise Interactions in Age-related Metabolic Muscle Dysfunction

Conditions
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Elderly Persons

Intervention / Treatment
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* Other: Hypoxic exercise
* Other: Normoxic Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 55 to 75 years of age body mass index: 20 - 35 kg/m2 weight stable during last 6 months before screening (weight change < 2% body weight) HOMA-index of insulin resistance ≥ 2 to 4 units Exclusion Criteria: more than 1 hour of scheduled exercise training per week known diagnosis of type 2 diabetes or measured HbA1c > 6,5% known drug or alcohol abuse any contraindication to perform exercise training acute or chronic infections increased bleeding risk by history, INR > 1,3, use of anticoagulants

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypoxic Exercise<br>Supervised, progressive aerobic exercise for 8 weeks under hypoxic conditions | Other: Hypoxic exercise<br>* Supervised, progressive aerobic exercise program for 8 weeks under hypoxic conditions<br>|
| Sham Comparator: Normoxic exercise<br>Supervised, progressive aerobic exercise for 8 weeks under normoxic conditions | Other: Normoxic Exercise<br>* Supervised, progressive aerobic exercise program for 8 weeks under normoxic conditions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Insulin sensitivity is assessed via the hyperinsulinemic euglycemic glucose clamp and expressed as the glucose infusion rate (GIR) in ml | At baseline and after 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum oxygen uptake | Maximum oxygen uptake is measured during an incremental exhaustive exercise test and is expressed in ml/min/kg | At baseline and after 8 weeks | 
| Mitochondrial number | Mitochondrial number and selected gene expression assessed from muscle biopsies from the vastus lateralis. | At baseline and after 8 weeks | 
| Fat and carbohydrate oxidation during exercise | Fat and carbohydrate oxidation during exercise is assessed during an incremental exercise test by measurements of gas exchange and expressed as g/min | At baseline and after 8 weeks | 
| Body fat and body fat free mass | Measured via by air-displacement plethysmography (ADP) and expressed in kg | At baseline and after 8 weeks | 
| Health related quality of life | Assessed using the short form 36 (SF-36) questionnaires | At baseline and after 8 weeks |